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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already surpassed the combined mortality inflicted by the severe acute respiratory syndrome (SARS) epidemic of 2002 and 2003 and the Middle East respiratory syndrome (MERS) epidemic of 2013. The pandemic is spreading at an exponential rate, with millions of people across the globe at risk of contracting SARS-CoV-2. Initial reports suggest that hypertension, diabetes, and cardiovascular diseases were the most frequent comorbidities in affected patients, and case fatality rates tended to be high in these individuals. In the largest Chinese study to date,1 which included 44 672 confirmed cases, preexisting comorbidities that had high mortality rates included cardiovascular disease (10.5%), diabetes (7.3%), and hypertension (6.0%). Patients with such comorbidities are commonly treated with renin angiotensin system blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). However, the use of ACEIs/ARBs in patients with COVID-19 or at risk of COVID-19 infection is currently a subject of intense debate. Below, we outline the mechanisms by which ACEIs/ARBs may be of benefit in those with COVID-19, what the current recommendations are for their use in infected patients, and suggested areas for further research.
SARS-CoV-2 uses the angiotensin-converting enzyme (ACE) 2 receptor for entry into target cells. ACE2 is predominantly expressed by epithelial cells of the lung, intestine, kidney, heart, and blood vessels. Both ACE and ACE2 belong to the ACE family of dipeptidyl carboxydipeptidases and exert distinct physiological functions. ACE cleaves angiotensin I to angiotensin II, which in turn binds and activates angiotensin II receptor type 1. This activation leads to vasoconstrictive, proinflammatory, and pro-oxidative effects. In contrast, ACE2 also degrades angiotensin II to angiotensin 1-7 and angiotensin I to angiotensin 1-9. When angiotensin 1-9 binds to the Mas receptor, it leads to anti-inflammatory, antioxidative, and vasodilatory effects. It is important to note that 2 forms of ACE2 exists: a structural transmembrane protein with extracellular domain that serves as a receptor for spike protein of SARS-CoV-2 and a soluble form that represents the circulating ACE2. Understanding the relationship between SARS-CoV-2 and membranous and soluble ACE2 may help us better understand the adaptive or maladaptive processes operative in COVID-19 infection.
Animal (mice) studies have shown that expression of ACE2 is substantially increased in patients treated with ACEIs/ARBs.2,3 Similar to these observations, higher urinary ACE2 levels were seen in patients with hypertension treated with the ARB olmesartan. In another study,4 circulating ACE2 levels were increased in patients with diabetes treated with ACEIs. Based on these observations, some experts have speculated that use of ACEIs/ARBs leading to increased expression of ACE2 could potentially facilitate infection with COVID-19.
Several professional societies have put forward their guidance regarding the use of ACEIs/ARBs in patients with COVID-19. In summary, all guidelines recommend continuing ACEIs/ARBs in patients with COVID-19 unless clinically indicated (Table). Furthermore, they do not suggest initiation of ACEIs/ARBs in those without another clinical indication (eg, hypertension, heart failure, diabetes), given the lack of strong evidence showing benefit of these medications in COVID-19. We agree with these recommendations, given the current state of evidence. However, the biological plausibility of salutary effects of ACEIs/ARBs in those with COVID-19 is intriguing. A multicenter, double-blind, placebo-controlled phase 2 randomized clinical trial of starting losartan in patients with COVID-19 in outpatient settings ( identifier: NCT04311177) and in in-patient settings ( identifier: NCT04312009) is currently being planned. Accordingly, further epidemiological studies and prospective trials are urgently needed to investigate if use of ACEIs/ARBs can reduce the incidence or mortality associated with COVID-19–associated ALI or ARDS, both in patients with and without additional clinical indications for ACEIs/ARBs.

As we brace for the imminent impact of the coronavirus disease 2019 (COVID-19) pandemic, we are faced with a controversy on how to best minimize the risk of lethal disease among the most vulnerable of us. Preliminary epidemiological data show an uneven-handed impact on the population, with an exponential increase in disease severity and mortality in those beyond the sixth decade of life with cardiovascular disease (CVD) and diabetes. Given that angiotensin-converting enzyme 2 (ACE2), an enzyme coopted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter epithelial cells, is upregulated in patients with CVD and diabetes treated with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), it was proposed that this increase in ACE2 expression underpins the greater COVID-19 severity in this population. This has created substantial controversy regarding the approach to patients taking ACEIs/ARBs in preparation for the pandemic, with some advocating for discontinuing these medications while expert opinions recommended against discontinuation, given the lack of strong evidence.1
To begin to unravel this complex dilemma, we must consider the role of ACE2 not only in COVID-19 pathogenesis but also as a component of renin-angiotensin system (RAS) signaling throughout the body. First, one must recognize the scarcity of data on the topic, particularly in humans. Nonetheless, the urgency of the situation makes it imperative to use inductive reasoning to guide our next steps toward protecting our patients. It is well established now that while ACE2 is targeted by SARS-CoV-2 to gain entrance into cells, it plays a major anti-inflammatory role in RAS signaling by converting angiotensin II, the quintessential perpetrator of inflammation,2 to angiotensin 1-7, which carries anti-inflammatory properties.3
What has been missing in discussions of the aforementioned dilemma is the age-associated decline in ACE2 expression, as observed in the lungs of rats,4 which is in line with a constellation of major proinflammatory changes perpetrated by an age-associated increase in RAS signaling throughout the body.5 Exaggerated forms of this proinflammatory profile are also salient pathophysiologic features of hypertension and diabetes, which are highly prevalent at older ages.5 The upregulation of ACE2 in individuals with diabetes and hypertension treated with ACEIs/ARBs is, in a way, restorative of physiological function. Hence, these observations raise an apparent paradox: given ACE2 itself is the gateway of SARS-CoV-2 entry into cells, how can the reduction in ACE2 levels in older persons and those with CVD predispose for greater COVID-19 severity?
This apparent paradox becomes clear if we distinguish the role of ACE2 as a gateway for SARS-CoV-2 facilitating the infection from its pivotal anti-inflammatory function in RAS signaling that is compromised in individuals with COVID-19, contributing to its severity (Figure).3 Indeed, data on the severe acute respiratory syndrome epidemic of 2003 demonstrates this divergence in factors predisposing to disease occurrence and its severity; in the former epidemic, although younger individuals in their third and fourth decades of life accounted for most of those infected,6 these younger patients had lower disease severity and risk of mortality compared with older people with preexisting conditions.
Simplified schematic of the preinfection inflammatory profile among predisposed older individuals vs their younger counterparts. ACE2 indicates angiotensin-converting enzyme 2; CVD, cardiovascular disease; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Similarly, in the COVID-19 pandemic, it is plausible that greater expression of ACE2 leads to higher predisposition to incur the disease; preliminary epidemiologic data from South Korea, where the most population-wide testing has taken place, show that most cases are among younger adults7 who are expected to have higher levels of ACE2.4 However, when it comes to COVID-19 severity, reduction in ACE2 levels with aging and CVD and its associated upregulation of angiotensin II proinflammatory pathway8 likely predispose older individuals with cardiovascular comorbidities to severe forms of COVID-19, as has been observed in Italy.7 This predisposition is exploited with SARS-CoV-2 binding to ACE2 itself, further reducing ACE2 cell surface expression, upregulating angiotensin II signaling in the lungs, and yielding acute lung injury.3 Hence, compared with young individuals, older persons with CVD who already have reduced ACE2 levels will be expected to be more predisposed to exaggerated inflammation with further reduction in ACE2 expression in the context of COVID-19, manifesting with greater disease severity.
In summary, older individuals, especially those with hypertension and diabetes, have reduced ACE2 expression and upregulation of angiotensin II proinflammatory signaling; the increase in ACE2 levels with ACEI/ARB treatment is more likely to be corrective to these changes. We hypothesize that with superimposed COVID-19 disease, SARS-CoV-2 binding to ACE2 acutely exaggerates this proinflammatory background, predisposing these subpopulations to greater COVID-19 disease severity and mortality (Figure). This hypothesis is in line with the evidence of a protective role of angiotensin II antagonism against sepsis-associated acute lung injury9,10 and supports continuing therapy with ACEIs/ARBs and, more so, urgently calls for expanding ongoing trials treating patients with severe COVID-19 with RAS interventions to examine the role of these interventions in preventing lethal lung complications of COVID-19 as cases surge around the world.

The emergence of a coronavirus illness not previously seen in humans, now called coronavirus disease 2019 (COVID-19), has captured the attention of the US and the world. The virus was first identified in Wuhan, China, after an outbreak of pneumonia of unknown cause was identified in December 2019, with most early cases reporting exposure to a live animal market. On December 31, 2019, China reported the outbreak to the World Health Organization, and shortly thereafter, the responsible pathogen was identified as a novel coronavirus, which is called SARS-CoV-2 because of its sequence similarity to the virus causing severe acute respiratory syndrome (SARS). The situation of COVID-19 is evolving rapidly with increasing numbers of cases and involved countries. On January 30, 2020, the World Health Organization declared the novel coronavirus outbreak a public health emergency of international concern, and on March 11, 2020, the outbreak was declared a pandemic. As of March 25, 2020, more than 425 000 cases have been confirmed globally in 170 countries and regions, including more than 55 000 cases in the United States.1
Coronaviruses cause a wide range of illness, ranging from the common cold to severe, fatal illness. Three coronaviruses causing severe illness in humans have emerged in the past 20 years: the virus causing SARS, which emerged in China in 2002; the virus causing Middle East respiratory syndrome (MERS), which emerged in the Arabian peninsula in 2012; and the virus causing COVID-19.2 Common manifestations of COVID-19 in adults include fever, cough, myalgia, shortness of breath, headache, and diarrhea. Based on data from more than 72 000 patients from China, most (81%) were mildly affected, 14% had severe manifestations (eg, with dyspnea or blood oxygen saturation ≤93%), and 5% were critically ill (eg, with respiratory failure or septic shock).3 Risk factors for severe illness were older age and underlying illnesses. The case fatality rate in China was 2.3%,3 although this number might be an overestimate because mild or asymptomatic cases might have been missed. Transmission of COVID-19 is thought to be primarily through respiratory droplets formed when a person with an infection coughs or sneezes, which can be inhaled by contacts within close range (within 6 ft), who then become infected. Other types of transmission (eg, transmission from fomites, fecal-oral transmission) might be possible. The median incubation period is 5 days (range, 2-14 days). At this time, care of patients with severe illness is supportive, since US Food and Drug Administration–approved therapeutics are not available. Although vaccine development is ongoing, it is expected that a vaccine will not be ready for wide distribution for at least a year.4
What Is Known About COVID-19 in Children?
Children are typically more susceptible to influenza complications, yet so far, they have experienced lower-than-expected rates of COVID-19 disease, and deaths in children appear to be rare. In more than 72 000 total cases from China, 1.2% were in patients aged 10 to 19 years, and even fewer (0.9%) were in patients younger than 10 years.3 Only 1 death in this study was in the adolescent age range, and no children in the age range of 0 to 10 years died. In a separate analysis of 2143 confirmed and suspected pediatric cases from China, infants were at the highest risk of severe disease (10.6%), compared with older children (4.1% for those aged 11 to 15 years; 3.0% in those 16 years and older).5
Among children who become ill, manifestations of COVID-19 appear to be similar to those in adults. Among 28 pediatric patients reported by Shen and Yang,6 age ranged from 1 month to 16 years. Several patients were asymptomatic at diagnosis and identified as part of contact investigations. Several patients had fever, fatigue, dry cough, and other respiratory symptoms; gastrointestinal manifestations were infrequent.
Transmission is likely the same as that seen in adults. Thus far, no convincing evidence of intrauterine transmission has been identified, but only a small number of pregnancies have been described.2 Whether COVID-19 can be transmitted through breastfeeding is unknown, to our knowledge. Among 6 mothers whose breastmilk samples were tested for SARS-CoV-2, all specimens were negative.2
Despite the low frequency of illness and death from COVID-19 in children in China, there are reasons to remain vigilant about infection in children. The lower-than-expected rates of children affected by COVID-19 in China might be because of decreased exposure to the virus, decreased infection with the virus because of immunity to other coronaviruses, or decreased likelihood of illness, even when infected with the virus. If children are infected but asymptomatic, they could serve as a source of transmission to adults. At least 1 child with no symptoms but with a high SARS-CoV-2 viral load has been reported,7 suggesting that transmission from children who are asymptomatic is possible.
How US children experience COVID-19 remains to be detailed, although no intensive care unit admissions or deaths were reported among persons younger than 19 years among 4226 patients with COVID-19 in the US through March 16, 2020.8 In a small study from China, 7 of 20 pediatric patients who were ill with COVID-19 had a prior history of a congenital or acquired disease,9 leading the authors to suggest the children with underlying illness might be more susceptible. About 10% of children in the US have asthma; many children live with other pulmonary, cardiac, neuromuscular, or genetic diseases that affect their ability to handle respiratory disease, and other children are immunosuppressed because of illness or its treatment. It is possible that these children will experience COVID-19 differently than counterparts of the same ages who are healthy.
Considerations for Pediatric Health Care Clinicians
Pediatric health care clinicians can help to prepare their offices, facilities, and communities for increased COVID-19 disease. Special accommodations should be made to isolate children who are potentially ill with COVID-19 from those who are well in the waiting room, especially focusing on minimizing exposures for those with special health care needs. In communities with widespread transmission, limiting healthy children from visiting the health care system for nonurgent reasons (eg, nonurgent surgeries) might be warranted, while continuing to see newborns and infants for preventive care and younger children who need vaccines. This action will necessitate robust telephone triage and expansion of existing telehealth visits. Differentiating potential COVID-19 illness from other illnesses, such as influenza, will be difficult until testing for COVID-19 becomes more broadly available. In communities with widespread transmission, community mitigation interventions, such as school closures, cancellation of mass gatherings, and closure of public places are appropriate.10 If these measures are required, pediatricians need to advocate to alleviate unintended consequences or inadvertent expansion of health disparities on children, such as by finding ways to maintain nutrition for those who depend on school lunches and provide online mental health services for stress management for families whose routines might be severely interrupted for an extended period of time.
In conclusion, COVID-19 is an emerging illness that is rapidly spreading through the US and the world. Early data suggest that the effects on children are less severe than those on adults, yet many questions remain, especially regarding the effects on children with special health care needs. Surveillance of COVID-19 in the pediatric population, including seroprevalence studies, is needed to better understand its influence on US children. Clinicians need to work with school and community leaders to implement interventions that slow disease spread and prevent severe illness and death, while ensuring that unintended consequences of these interventions on children are minimized.

Coronavirus disease 2019 (COVID-19) infection can be diagnosed using a test called polymerase chain reaction (PCR).
What Is the PCR Test for COVID-19 Infection?
Samples are taken from places likely to have the virus that causes COVID-19, like the back of the nose or mouth or deep inside the lungs. After a sample is collected, RNA, which is part of the virus particle, is extracted and converted to complementary DNA for testing. The PCR test involves binding sequences on the DNA that only are found in the virus and repeatedly copying everything in between. This process is repeated many times, with doubling of the target region with each cycle. A fluorescent signal is created when amplification occurs, and once the signal reaches a threshold, the test result is considered positive. If no viral sequence is present, amplification will not occur, resulting in a negative result.
Should You Be Tested?
Guidelines for testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, continue to evolve as knowledge of COVID-19 improves and availability of testing increases. Currently, testing in the US is only performed for individuals when a positive result will change treatment. Testing is also prioritized for people who have a high risk for bad outcomes from COVID-19 infection, such as elderly or immunosuppressed patients, and those with high risk of exposure and transmission of the disease to other people, such as health care workers. Recommendations for testing are regularly updated by the Centers for Disease Control and Prevention (CDC). If you have questions about testing, contact your local public health department.
Why Has Adoption of Testing Been Slow in the US?
Regulatory process and time required to validate clinical tests. The regulatory process in the US is designed to ensure patient safety and accurate diagnostic testing. Testing was initially only offered through an assay developed by the CDC; however, only a limited number of test kits were available. Alternate tests required Emergency Use Authorization from the US Food and Drug Administration before use. This policy was changed on February 29, 2020, to allow use of tests before approval, which has improved access.
Initial lack of certified laboratories with PCR capabilities. Most clinical laboratories did not have the capability to perform PCR at the beginning of the outbreak. Skilled laboratories and technicians are needed for PCR, as contamination at any step drastically changes results.
Shortage of chemicals and supplies. Certain chemicals and supplies, such as those used in extraction and PCR kits, were initially in short supply. Reagents have become more available as alternative PCR tests are developed. Personal protective equipment for technicians handling specimens has also been limited.
Are Alternative Tests Available?
Blood antibody testing and viral antigen testing in respiratory samples, similar to the rapid influenza test, are currently being investigated. The clinical value of these tests is not known yet, and challenges such as cross-reactivity with other viruses, and that sometimes the test does not detect the virus when it is there, need to be addressed.
Centers for Disease Control and Prevention. Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19)

According to the WHO coronavirus disease (COVID-19) situation report 35, as of 24th February 2020, there was a total of 77,262 confirmed COVID-19 cases in China. That included 2595 deaths. The specific objective of this study was to estimate the fiscal value of human lives lost due to COVID-19 in China as of 24th February 2020. The deaths from COVID-19 had a discounted (at 3%) total fiscal value of Int$ 924,346,795 in China. Out of which, 63.2% was borne by people aged 25–49 years, 27.8% by people aged 50–64 years, and 9.0% by people aged 65 years and above. The average fiscal value per death was Int$ 356,203. Re-estimation of the economic model alternately with 5% and 10 discount rates led to a reduction in the expected total fiscal value by 21.3% and 50.4%, respectively. Furthermore, the re-estimation of the economic model using the world’s highest average life expectancy of 87.1 years (which is that of Japanese females), instead of the national life expectancy of 76.4 years, increased the total fiscal value by Int$ 229,456,430 (24.8%).

Since December 2019, coronavirus disease 2019 (COVID-19) has been reported among patients in China. Currently, the disease is quickly spreading worldwide. The pathogen of COVID-19 is a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), identified as a member of the Coronaviridae family. Another coronavirus, named SARS-CoV-1, was responsible for severe acute respiratory syndrome.1 Compared with SARS-CoV-1, SARS-CoV-2 has a similar binding receptor and similar pathologic features systemically and epidemiological characteristics.1,2 Although there is no direct evidence that SARS-CoV-1 replication results in conjunctivitis and other ocular diseases, reports have emphasized the eye as a potential site for virus transmission.3 Similarly, SARS-CoV-2 transmission through the eye has been suspected.
Nevertheless, there are no reports in the medical literature at this time, to our knowledge, that identify a direct relationship between SARS-CoV-2 and the eye. Researchers have not reported ocular abnormalities nor have they stated in the medical literature if there was conjunctivitis or viral presence detected in the tears of patients with COVID-19. The objective of this study was to evaluate ocular involvement systematically in patients highly suspected of having or confirmed to have COVID-19.
Of the 38 consecutive patients with COVID-19 who were recruited, 25 (65.8%) were male, and the mean (SD) age was 65.8 (16.6) years (Table 1). Among them, 28 patients (73.7%) had positive findings for COVID-19 on RT-PCR from nasopharyngeal swabs, and of these, 2 patients (5.2%) yielded positive findings for SARS-CoV-2 in their conjunctival as well as nasopharyngeal specimens. The other 10 patients who were hospitalized were judged to have COVID-19 by the guideline of PC-NCP,4 with fever and/or respiratory symptoms and lung computed tomography imaging features of COVID-19 pneumonia.
A total of 12 of 38 patients (31.6%; 95% CI, 17.5-48.7) had ocular manifestations consistent with conjunctivitis, including conjunctival hyperemia, chemosis, epiphora, and increased secretions (Table 2). Among these 12 patients, there were 4 cases judged as moderate, 2 cases judged as severe, and 6 cases judged as critical, which was graded according to the guideline of PC-NCP4: moderate indicated fever and/or respiratory symptoms and lung computed tomography imaging findings; severe indicated dyspnea (respiratory frequency of 30 cycles per minute or greater), blood oxygen saturation of 93% or less, and an arterial partial pressure of oxygen to fraction of oxygen inspiration ratio of 300 or less; and critical indicated respiratory failure or shock or multiple organ dysfunction/failure.4 In these patients, 1 patient experienced epiphora as the first symptom of COVID-19. None of them experienced blurred vision. By univariate analysis, patients with ocular symptoms were more likely to have higher white blood cell and neutrophil counts and higher levels of procalcitonin, C-reactive protein, and lactate dehydrogenase than patients without ocular symptoms (Table 1). In addition, 11 of 12 patients with ocular abnormalities (91.7%; 95% CI, 61.5-99.8) had positive results for SARS-CoV-2 on RT-PCR from nasopharyngeal swabs. Of these, 2 (16.7%) had positive results for SARS-CoV-2 on RT-PCR from both conjunctival and nasopharyngeal swabs.
Few previous investigations have evaluated ocular signs and symptoms in patients infected with SARS-CoV-1 and SARS-CoV-2. A few reports have evaluated for the presence of SARS-CoV-2 in tear fluid.3,5 Our investigation suggests that among patients with COVID-19, 31.6% (95% CI, 17.5-48.7) have ocular abnormalities, with most among patients with more severe systemic manifestations or abnormal findings on blood tests. These results suggest that ocular symptoms commonly appear in patients with severe pneumonia.
Our results show a low prevalence (5.2%; 95% CI, 0.6-17.8) of SARS-CoV-2 nucleotides in conjunctival specimens of patients with COVID-19, consistent with previous studies on severe acute respiratory syndrome.3 Of note, we found only 1 patient presenting with conjunctivitis as the first symptom. Previous reports have shown the shedding of potentially infectious virus can occur in people who have no fever and minor or absent signs of infection.6 Because unprotected eyes were associated with an increased risk of transmission of SARS-CoV-1,7 in support of our current results, our results might suggest that SARS-CoV-2 might be transmitted through the eye.
Limitations of this study include a relatively small sample size and absence of detailed ocular examinations to exclude intraocular disease owing to the logistical challenges of managing these patients at this time. In addition, we only sampled once from the eye of each patient, which can decrease the prevalence owing to false-negatives. Regardless, these preliminary results are shared in an effort to inform ophthalmologists and others around the world regarding ocular symptoms with COVID-19.
Accepted for Publication: March 17, 2020.
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank Haijiang Zhang, MD, Minxing Wu, MD, and Min Liu, MD (Yichang Central People’s Hospital, Yichang, China), for collecting the data and preparing the Table. None of these individuals received compensation for their contributions.

The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell–cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.