The COVID-19 pandemic

Abstract

In December 2019, an outbreak of pneumonia of unknown origin was reported in Wuhan, Hubei Province, China. Pneumonia cases were epidemiologically linked to the Huanan Seafood Wholesale Market. Inoculation of respiratory samples into human airway epithelial cells, Vero E6 and Huh7 cell lines, led to the isolation of a novel respiratory virus whose genome analysis showed it to be a novel coronavirus related to SARS-CoV, and therefore named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus belonging to the subgenus Sarbecovirus. The global spread of SARS-CoV-2 and the thousands of deaths caused by coronavirus disease (COVID-19) led the World Health Organization to declare a pandemic on 12 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. In this review, we provide information regarding the epidemiology, serological and molecular diagnosis, origin of SARS-CoV-2 and its ability to infect human cells, and safety issues. Then we focus on the available therapies to fight COVID-19, the development of vaccines, the role of artificial intelligence in the management of the pandemic and limiting the spread of the virus, the impact of the COVID-19 epidemic on our lifestyle, and preparation for a possible second wave.

Keywords: 

• SARS-CoV-2
• rRT-PCR
• COVID-19
• cytokine storm
• pneumonia
• ACE2
• serology

Previous articleView issue table of contentsNext article

1. Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the seventh human coronavirus, was discovered in Wuhan, Hubei province, China, during the recent epidemic of pneumonia in January 2020 [1,2]. Since then, the virus has spread all over the world, and as of 20 May 2020, it has infected 4,806,299 people, and caused 318,599 deaths [3]. SARS-CoV-2 as well as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) cause severe pneumonia with a fatality rate of 2.9%, 9.6% and ∼36%, respectively [4–6]. The other four human coronaviruses, OC43, NL63, HKU1 and 229E, generally cause self-limited disease with mild symptoms [7].

In this review, we summarize the state of art of COrona VIrus Disease 19 pandemic (COVID-19, as defined by the World Health Organization [WHO] in February 2020), including the origin of SARS-CoV-2, its ability to infect human cells, epidemiology, clinical pathological and laboratory findings, molecular and serological diagnosis and safety issues. We also provide information on available therapies, vaccine development, and the potential role of artificial intelligence in the governance of health care systems and its usefulness in fighting the COVID-19 outbreak.

2. Origin of SARS-CoV-2

Since the discovery of the novel coronavirus, SARS-CoV-2, scientists have debated its origin [8]. It has been speculated that SARS-CoV-2 is the product of laboratory manipulations. However, genetic data does not support this hypothesis and shows that SARS-CoV-2 did not derive from a previously known virus backbone [9].

Genomes analysis and comparison with previously known coronavirus genomes indicate that SARS-CoV-2 presents unique features that distinguish it from other coronaviruses: optimal affinity for angiotensin converting enzyme 2 (ACE2) receptor and a polybasic cleavage site at the S1/S2 spike junction that determines infectivity and host range [8,10].

SARS-CoV-2 is highly similar to bat SARS-like coronaviruses [2] and bat might be the reservoir host. RaGT13 is ∼96% identical to SARS-CoV-2 with some differences in the spike receptor binding domain (RBD) that could explain the differences in ACE2 affinity between SARS-CoV-2 and SARS-like coronaviruses.

The polybasic cleavage site of SARS-CoV-2 is not present in pangolin beta-coronavirus, which share similarities with SARS-CoV-2. Also, the sequence of RBD of the spike protein (S) suggests that it arose from a natural evolutionary process [8].

Estimates of the most recent common ancestor of SARS-CoV-2 date the epidemic to between late November 2019 and the beginning of December 2019, which is compatible with the first reported cases [11]. Thus, there was unnoticed human transmission after the zoonotic event and before the acquisition of the polybasic furin cleavage site [8].

3. Epidemiology

3.1. Disease presentation

Patients with SARS-CoV-2 infection may present symptoms ranging from mild to severe with a large portion of the population being asymptomatic carriers. The most common reported symptoms include fever (83%), cough (82%) and shortness of breath (31%) [12]. In patients with pneumonia, chest X-ray usually shows multiple mottling and ground-glass opacity [12,13].

Gastrointestinal symptoms such as vomiting, diarrhea, and abdominal pain are described in 2–10% of the patients with COVID-19 [12,14], and in 10% of patients, diarrhea and nausea precede the development of fever and respiratory symptoms [12].

COVID-19 patients usually show decrease lymphocyte and eosinophils counts, lower median hemoglobin values as well as increases in WBC, neutrophil counts, and serum levels of CRP, LDH, AST, and ALT [15]. Moreover, initial CRP serum levels have been reported to be an independent predictor for the development of severe COVID-19 infection [16,17].

Although the main target of coronavirus infection is the lung, the wide distribution of ACE2 receptors in organs [18] may lead to cardiovascular, gastrointestinal, kidney, liver, central nervous system and ocular damage that has to be closely monitored [19].

The cardiovascular system is often affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events, and monitoring with high sensitivity cardiac troponin may be useful [20].

Patients presenting with acute respiratory distress syndrome may worsen rapidly and die of multiple organ failure [12] induced by the so-called “cytokine storm”.

Indeed, a cytokine profile resembling the secondary hemophagocytic lymphohistiocytosis syndrome has been described in severe COVID-19 cases, and is characterized by increased interleukin (IL)-2, IL-7, granulocyte colony stimulating factor, interferon-γ inducible protein-10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumor necrosis factor-α [11]. In addition, elevated levels of ferritin and IL-6 are predictors of fatality, and death is likely due to hyperinflammation induced by the virus [21]. Based on this evidence, tocilizumab (IL-6 receptor blockade) is administered to patients with COVID-19 pneumonia and elevated serum IL-6 to reduce inflammation in the lungs.

Elevation of D-dimer levels has been associated with the severity of COVID-19. Subjects with severe COVID-19 have significantly higher values of D-dimer than those without (weighted mean difference 2.97 mg/L; 95% CI: 2.47–3.46 mg/L) [22]. The elevated D-dimer levels may reflect the risk of disseminated coagulopathy in patients with severe COVID-19, which may require anticoagulant therapy [22].

The Italian Agency of Medicine (AIFA) has recently approved a clinical trial (INHIXACOVID19 study) in which enoxeparin is given subcutaneously to patients with COVID-19 to prevent thromboembolism-related complications. Heparin also has antiviral activity. It is known for its ability to prevent viral infection including coronaviruses infection. Indeed, heparin has a structure similar to that of heparan sulfate that is present on mammalian cellular surfaces and that is utilized by coronaviruses to enter cells [23,24]. In the presence of heparin, the interaction of the S protein with heparan sulfate may be blocked, thus preventing cell entry.

Furthermore, heparin may inhibit proteases involved in virus infectivity [25]. Indeed, SARS-CoV-2 entry requires the cleavage of the S1–S2 subunits followed by the fusion of S2 to the cell membrane. The latter requires the action of host proteases such as cathepsins, cell surface transmembrane protease/serine proteases (TMPRSS), furin, trypsin and factor Xa that are inhibited by heparin.

The course of COVID-19 disease in children is generally asymptomatic or mild compared to that seen in adults, for reasons that are yet to be clearly elucidated. Nonetheless, severe and fatal cases have been reported in children. Clinical laboratory data in children is quite different from adults as reported in a recent meta-analysis that showed an inconsistent alteration of the leukocyte index [26]; however, elevations in the levels of CRP, procalcitonin and LDH were also found in children with severe disease. Interestingly, creatine kinase-MB was elevated in one-third of patients and this raised the suspicion of cardiac involvement in COVID-19 pediatric patients, as recently reported [27].

3.2. SARS-COV-2 transmission

As with other respiratory viruses, SARS-CoV-2 transmission occurs with high efficacy and infectivity mainly through the respiratory route. Droplet transmission is the main recognized route, although aerosols may represent another important route [28,29]. Estimates of the reproduction number (R0) of SARS-CoV-2 range from 1.4 to 2.5 [Statement on the meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV), https://www.who.int/news-room/detail/23-01-2020-statement-on-the-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov)] to 2.24–3.58 [30].

Similar to SARS-CoV, the oral-fecal route may be another route of transmission of the virus. SARS-CoV-2 RNA has been detected in the stool of patient with COVID-19 pneumonia [31]. Therefore, sewage may have a role in the transmission of SARS-CoV-2. In light of that, technical treatment such as biosorbents capable of retaining and inactivating the virus should be considered [32].

SARS-CoV-2 has been detected in saliva of infected individuals [33]; this can be attributed to the presence of ACE2 receptors in epithelial cells lining the salivary gland ducts [34].

In some studies, patient urine has been tested for SARS-CoV-2 viral RNA. Amongst these studies, the pooled rate of RNA positivity was about 5–6%; nevertheless, the duration of viral shedding in urine samples as well as the infectivity of urine remains to be established [35].

SARS-CoV-2 RNA has also been detected on inanimate surfaces such as door handles and the surface of cell phones in residential sites of patients with confirmed COVID-19. Thus, individuals who have come into contact with infected surfaces could be infected if they touch their eyes, mouth or nose [29].

The vertical transmission of SARS-CoV-2 is debated; a series of nine pregnant women with confirmed COVID-19 showed no mother to child transmission. In addition, SARS-CoV-2 was not detected in breast milk, indicating that the virus cannot be transmitted with breastfeeding [36]. Nevertheless, a newborn with elevated IgM against SARS-CoV-2 born to a mother with COVID-19 has been recently reported. IgM antibodies along with IgG antibodies were detected 2 h after delivery. Il-6 and IL-10 were also elevated, while polymerase chain reaction (PCR) performed on consecutive nasopharyngeal swabs from 2 h to 16 days of age was always negative. Considering that IgM cannot cross the placenta and be transferred to the fetus, it could be hypothesized that the infant was infected in utero even if amniotic fluid was not tested for SARS-CoV-2 RNA [37].

Finally, the eyes may be a route of transmission of SARS-CoV-2. SARS-CoV-2 RNA was detected in ocular swabs of a patient with confirmed COVID-19 3 days after onset of symptoms and at 27 days when a nasopharyngeal swab tested negative by PCR. Interestingly, the virus from an ocular swab was propagated in Vero E6 cells, suggesting that ocular secretions could be infectious [38]. Although no conclusive data is available, goggles should be worn when examining patients with suspected or confirmed COVID-19 [39].

3.3. SARS-CoV-2 incubation period

Determination of the incubation period of SARS-CoV-2 infection is crucial for determining the duration of quarantine, to evaluate the efficacy of entry screening and contact tracing. Based on a Weibull distribution, it was estimated that the mean incubation period is 6.4 days (95% confidence interval (CI): 5.6–7.7), with a range of 2.1–11.1 days (2.5th–97.5th percentile) [40]. Similar estimates have been made by other authors. In a study by Lauer et al. [41], it was estimated that the median incubation period was 5.1 days (95% CI, 4.5–5.8 days), and that 97.5% of infected individuals would develop symptoms within 11.5 days (CI, 8.2–15.6 days) of infection. Therefore, the 14-day period of active monitoring recommended by health authorities is justified by the evidence [42,43]. Longer monitoring can be required in particular cases. It was estimated that 101 out of every 10,000 cases (99th percentile, 482) may develop symptoms after 14 days of active monitoring or quarantine [41].

4. Viral testing

4.1. Reverse real-time PCR assays

Suspected cases of SARS-CoV-2 infection are confirmed by detection of specific and unique viral sequences using a reverse real-time PCR (rRT-PCR) assay. Immediately after the declaration by the Chinese Health Authorities, on 7 January 2020, that the pneumonia outbreak in Wuhan was caused by a novel coronavirus, a European network of laboratories developed an rRT-PCR protocol based on the alignment and comparison of available bat-related coronavirus and SARS-CoV genome sequences plus five sequences from the novel coronavirus SARS-CoV-2 that were released by the Chinese authorities [44]. Three rRT-PCR assays were developed. The first line assay targets the E gene common to the coronaviruses belonging to Sarbecovirus subgenus and encoding the envelope protein. The second assay targets the RdRp gene encoding the RNA-dependent-RNA-polymerase. This assay contains two molecular probes: one reacts with the SARS-CoV and SARS-CoV-2 RdRp gene, while the second one (RdRP_SARSr-P2) reacts with SARS-CoV-2 RdRp gene. The third assay targets the N (nucleocapsid) gene. This protocol was adopted in 30 European countries [45].

Recently, a new PCR protocol targeting a different region of the RdRp/Hel gene showed a higher sensitivity and specificity than the RdRP_SARSr-P2 assay [46].

The US Centers for Disease Control and Prevention (CDC) protocol targets the N gene of SARS-CoV-2. Two primer/probe sets directed toward different regions of N gene were selected. In addition, a primer/probe set that detects the human RNase P gene in control samples and clinical specimens is included (https://www.fda.gov/media/134922/download. Revision 3, 30 March 2020).

Although amplification tests are sensitive, some infections are missed. The reasons for this may be the quality of the collected specimen, time of collection (very early phase of infection or too late during infection), viral load below the limit of detection of the assay, incorrect handling of the specimen or shipping issues. In the case of low viral load in the upper respiratory tract, a deeper specimen may be required to make a diagnosis [47]. Indeed, in SARS and MERS patients, viral RNA in the upper respiratory tract peaked in the first 7–10 days after symptoms onset, while in the lower respiratory tract, viral RNA was still detected 2–3 weeks after disease onset [47,48]. Repeat testing can also be performed in the case of nasopharyngeal swabs initially being negative as this increases the chance of detecting SARS-CoV-2 in the nasopharynx [49].

Several real-time PCR assays obtained the CE mark for in vitro diagnostics and are available on the market. Table 1 summarizes the gene targets, the technical features of the assays and the validated specimen types of the real-time PCR assays cleared by the Italian Ministry of Health.

Table 1. Real-time PCR assays cleared by the Italian Ministry of Health for detection of SARS-CoV-2.

Download CSVDisplay Table

Point of care tests (POCT) such as Xpert^® Xpress SARS-CoV-2 (Cepheid, Sunnyvale, CA, USA) QIAstat-Dx Respiratory 2019-nCoV Panel (QIAGEN, Hilden, Germany), and Simplexa™ COVID-19 Direct kit (DiaSorin Molecular LLC, Cypress, CA, USA) deliver results in about 30-60 min. They do not require skilled technicians and the hands-on time is less than 1 min. These tests can be very useful when clinicians have to make rapid treatment decisions.

A sensitive rRT-PCR assay could be performed on pooled samples. In the present situation where shortage of reagents can be a problem, sample pooling can be a valid alternative to allow the screening of a large number of people in a short time frame. In a recent study, a positive single sample could be detected in a pool of up 32 samples with an estimated false negative rate of 10% [50]. Pooled screening could be implemented to detect SARS-CoV-2 in the community [50,51].

A recent paper showed that in confirmed COVID-19 patients, saliva may be a more sensitive specimen for SARS-CoV-2 detection than nasopharyngeal swab. The authors also reported less variability in self-sample collection of saliva compared to nasopharyngeal swabs. This observation could open the way to at-home self-administered sample collection for large-scale screening of SARS-CoV-2 [52].

The use of urine for diagnostic purposes is still the object of debate. The receptor ACE2, which is used by SARS-CoV-2 to infect human cells, is present not only in the respiratory tract but also in the urogenital system: renal proximal tubule cells, bladder urothelial cells, Leydig cells and cells in the testicular seminiferous ducts in testis [53]. Indeed, patients with COVID-19 may present with kidney damage (proteinuria, elevated serum creatinine, high urea) or severe acute kidney failure. Damage to the reproductive system may occur as well [53]. Taken together, these data suggest that the urogenital system may represent a route of transmission of SARS-CoV2. Some authors reported the identification of the virus in urine [54]. Nevertheless, to date, there is insufficient evidence that urine can be used as a biological specimen for COVID-19 diagnosis.

4.2. CRISPR-Cas12-based lateral flow assay for detection of SARS-CoV-2

Recently, a CRISPR-Cas12-based assay called SARS-CoV-2 DNA endonuclease-targeted CRISPR Trans Reporter (DETECTR) has been developed for the diagnosis of SARS-CoV-2 infection. This assay performs simultaneous reverse transcription and isothermal amplification of RNA extracted from nasopharyngeal or oropharyngeal swabs using loop-mediated amplification (RT-LAMP) [55], followed by Cas12 detection of coronavirus sequences. Detection of the virus is confirmed by cleavage of a reporter molecule. The assay targets the E and N regions but unlike the CDC assay, this one does not target the N1 and N3 regions. Amplification of the E region allows the identification of three SARS-like coronaviruses [SARS-CoV-2 (accession NC_045512), bat SARS-like coronavirus (bat-SL-CoVZC45, accession MG772933) and SARSCoV (accession NC_004718)], whereas the N region specifically detects SARS-CoV-2.

The DETECTR assay can be run in 30–40 min and is visualized on a lateral flow strip. The test is positive if both E and N genes are detected or presumptive positive if either E or N gene is detected. The limit of detection (LOD) of this DETECTR assay is 10 copies/µl vs 1 copy/µl for the CDC assay. The positive predictive agreement and the negative predictive agreement of DETECTR assay versus the CDC assay were 95% and 100%, respectively [56].

4.3. Viral load in respiratory samples

Viral load determination performed on nasopharyngeal swabs demonstrated that mild clinical cases had a lower viral load in their respiratory specimens compared with severe cases. The mean viral load in severe cases was 60-fold higher than mild cases. Stratification of the data in relation at the time of sampling after disease onset showed that delta cycle threshold (delta Ct) values were significantly lower in severe cases than mild cases in the first 12 days of disease. In mild cases, viral clearance occurred earlier and after 10 days, 90% of the patients repeatedly tested negative by PCR. By contrast, PCR was still positive at day 10 or beyond in all severe cases. These preliminary data suggest that determination of SARS-CoV-2 load may be useful for monitoring the patients with COVID-19 disease and for predicting prognosis and assessing disease severity [57].

5. Serology

Several serological assays, including enzyme-linked immunosorbent assays (ELISA), chemiluminescence assays (CLIA), rapid antibody tests, and western blotting, have been developed since the beginning of the SARS-CoV-2 pandemic. The ELISA test developed by Wantai Biological Pharmacy Enterprise Co. (Beijing, China) detects total antibody, IgM and IgG against SARS-CoV-2 [58]. Total antibodies were detected based on a double-antigen sandwich immunoassay using recombinant antigens containing the RBD of the S protein of SARS-CoV-2 as the immobilized antigen and horse radish peroxidase (HRP) as the conjugated antigen. The IgM μ-chain capture method was used to detect IgM antibodies (IgM-ELISA), using the same HRP-conjugate RBD antigen as in the double-antigen sandwich immunoassay. The IgG antibodies were detected by an indirect ELISA test (IgG-ELISA) based on the recombinant nucleoprotein antigen. The specificity of the assays was determined by testing plasma samples of healthy individuals collected before the SARS-CoV-2 outbreak, and was 99.1%, 98.6% and 99.0% for total antibody, IgM and IgG, respectively [58]. Comparing the results obtained by real-time PCR with those generated by the antibody assays in the first week of illness, PCR showed a higher sensitivity than antibodies assays, 66.7% vs 38.3%. However, from days 8 to 12, the sensitivity of the antibody tests overtook that of the RNA test, and in the late phase of disease, the sensitivity of the antibody tests increased even further compared to the RNA test [58]. Nevertheless, to date, all the international professional organizations, the US Food and Drug Administration and the CDC do not recommend that serology tests be used for diagnosis.

Other research groups developed ELISA assays that used as antigens a modified full-length S protein and the RBD of SARS-CoV2. Using this approach, COVID-19 seroconverters were identified as early as 3 days post symptom onset. Similarly, an antibody test designed to detect E and N antigens detected IgM within one week from disease onset. IgM was detectable for about a month and then gradually disappeared, while IgG was detected after 10 days and was detected for a longer period of time [59].

Using a magnetic chemiluminescence enzyme immunoassay, 100% of patients with COVID-19 were found to be IgG positive 19 days after symptom onset. The median day for both IgG and IgM seroconversion was 13 days post symptoms. Seroconversion for IgM and IgG occurred simultaneously or sequentially. Three groups of patients were identified: patients with synchronous seroconversion of IgG and IgM, patients with IgM seroconversion earlier than IgG seroconversion, and patients with IgG seroconversion earlier than IgM seroconversion. IgM and IgG plateaued 6 days after the first determination. Interestingly, screening of close contacts of patients with COVID-19 showed that few individuals with negative RT-PCR and no symptoms tested positive to IgG and/or IgM, confirming that serology can help in obtaining better estimates of the spread of SARS-CoV-2 [60].

Display full size

Acknowledgements

Italy was the first country engaged in fighting SARS-CoV-2 pandemic after China. This is the reason we wrote this review with our Chinese colleagues. We thank them for their support that came from their experience, for their scientific contribution, and for their friendship.

Disclosure statement

No potential conflict of interest was reported by the author(s).

References

1. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
2. Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020; 579(7798):265–269. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
3. World Health Organization Coronavirus Disease 2019 (COVID-19) Situation Report-97. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200426-sitrep-97-covid-19.pdf[Google Scholar]
4. Wang C, Horby PW, Hayden FG, et al. A novel coronavirus outbreak of global health concern. Lancet. 2020;395(10223):470–473. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
5. Hui DSC, Zumla A. Severe acute respiratory syndrome: historical, epidemiologic, and clinical features. Infect Dis Clin North Am. 2019;33(4):869–889. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
6. Azhar EI, Hui DSC, Memish ZA, et al. The Middle East respiratory syndrome (MERS). Infect Dis Clin North Am. 2019;33(4):891–905. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
7. Corman VM, Muth D, Niemeyer D, et al. Hosts and sources of endemic human coronaviruses. Adv Virus Res. 2018;100:163–188. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
8. Andersen KG, Rambaut A, Lipkin WI, et al. The proximal origin of SARS-CoV-2. Nat Med. 2020;26:450–452. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
9. Almazán F, Sola I, Zuñiga S, et al. Coronavirus reverse genetic systems: infectious clones and replicons. Virus Res. 2014;189:262–270. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
10. Nao N, Yamagishi J, Miyamoto H, et al. Genetic predisposition to acquire a polybasic cleavage site for highly pathogenic avian influenza virus hemagglutinin. mBio. 2017;8(1):e02298. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
11. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
12. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
13. Zhu N ,Zhang D ,Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
14. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
15. Lippi G, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin Chem Lab Med. 2020;58(7):1063–1069. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
16. Bhargava A, Fukushima EA, Levine M, et al. Predictors for severe COVID-19 infection. Clin Infect Dis. 2020. DOI:10.1093/cid/ciaa674 [Crossref], [Google Scholar]
17. Wang CZ, Hu SL, Wang L, et al. Early risk factors of the exacerbation of coronavirus disease 2019 pneumonia. J Med Virol. 2020. DOI:10.1002/jmv.26071 [Crossref], [Web of Science ®], [Google Scholar]
18. Hamming I, Timens W, Bulthuis ML, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–637. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
19. Renu K, Prasanna PL, Valsala Gopalakrishnan A. Coronaviruses pathogenesis, comorbidities and multi-organ damage – a review. Life Sci. 2020;255:117839. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
20. Long B, Brady WJ, Koyfman A, et al. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020. DOI:10.1016/j.ajem.2020.04.048 [Crossref], [Web of Science ®], [Google Scholar]
21. Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–848. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
22. Lippi G, Favaloro EJ. D-dimer is associated with severity of coronavirus disease 2019: a pooled analysis. Thromb Haemost. 2020;120(05):876–878. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
23. Lang J, Yang N, Deng J, et al. Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans. Plos One. 2011;6(8):e23710. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
24. Vicenzi E, Canducci F, Pinna D, et al. Coronaviridae and SARS-associated coronavirus strain HSR1. Emerging Infect Dis. 2004;10(3):413–418. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
25. Belen-Apak FB, Sarialioglu F. The old but new: can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARSCoV2 by inhibition of host cell proteases? Med Hypotheses. 2020;142:109743. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
26. Henry BM, Benoit SW, Santos de Oliveira MH, et al. Laboratory abnormalities in children with mild and severe coronavirus disease 2019 (COVID-19): a pooled analysis and review. Clin Biochem. 2020.;81:1–8. DOI:10.1016/j.clinbiochem.2020.05.012 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
27. Sanna G, Serrau G, Bassareo PP, et al. Children’s heart and COVID-19: Up-to-date evidence in the form of a systematic review. Eur J Pediatr. 2020. DOI:10.1007/s00431-020-03699-0 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
28. Leung NHL, Chu DKW, Shiu EYC, et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nature Med. 2020;26(5):676–680. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
29. Han Q, Lin Q, Ni Z, et al. Uncertainties about the transmission routes of 2019 novel coronavirus. Influenza Other Respir Viruses. 2020;14(4):470–471. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
30. Zhao S, Lin Q, Ran J, et al. Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: a data-driven analysis in the early phase of the outbreak. Int J Infect Dis. 2020;92:214–217. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
31. Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382(10):929–936. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
32. Núñez-Delgado A. What do we know about the SARS-CoV-2 coronavirus in the environment? Sci Total Environ. 2020;727:138647. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
33. To KK, Tsang OT, Chik-Yan Yip C, et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis. 2020. DOI:10.1093/cid/ciaa149 [Crossref], [Web of Science ®], [Google Scholar]
34. Liu L, Wei Q, Alvarez X, et al. Epithelial cells lining salivary gland ducts are early target cells of severe acute respiratory syndrome coronavirus infection in the upper respiratory tracts of rhesus macaques. J Virol. 2011;85(8):4025–4030. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
35. Chan VW, Chiu PK, Yee CH, et al. A systematic review on COVID-19: urological manifestations, viral RNA detection and special considerations in urological conditions. World J Urol. 2020. DOI:10.1007/s00345-020-03246-4 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
36. Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395(10226):809–815. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
37. Dong L, Tian J, He S, et al. Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA. 2020;323(18):1846–1848. [PubMed], [Web of Science ®], [Google Scholar]
38. Colavita F, Lapa D, Carletti F, et al. SARS-CoV-2 isolation from ocular secretions of a patient with COVID-19 in Italy with prolonged viral RNA detection. Annals Intern Med. 2020. DOI:10.7326/M20-1176 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
39. Lu CW, Liu XF, Jia ZF. 2019-nCoV transmission through the ocular surface must not be ignored. Lancet. 2020;395(10224):e39. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
40. Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020. Euro Surveill. 2020;25(5):2000062. [Crossref], [Google Scholar]
41. Lauer SA, Grantz KH, Bi Q, et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med. 2020;172(9):577–582. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
42. The White House. Press Briefing by Members of the President’s Coronavirus Task Force. [cited 2020 Jan 31]. Available from: whitehouse.gov/briefings-statements/press-briefing-members-presidents-coronavirus-task-force[Google Scholar]
43. European Centre for Disease Prevention and Control. Algorithm for the management of contacts of probable or confirmed COVID-19 cases. [cited 2020 Feb 25]. Available from: https://www.ecdc.europa.eu/en/publications-data/algorithm-management-contacts-probableor-confirmed-covid-19-cases. [Google Scholar]
44. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3):2000045. [Crossref], [Google Scholar]
45. Reusken C, Broberg EK, Haagmans B, et al. Laboratory readiness and response for novel coronavirus (2019-nCoV) in expert laboratories in 30 EU/EEA countries. Euro Surveill. 2020;25(6):2000082. [Crossref], [Google Scholar]
46. Chan JF, Yip CC, To KK, et al. Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-polymerase chain reaction assay validated in vitro and with clinical specimens. J Clin Microbiol. 2020;58(5):pii: e0031020. [Crossref], [Web of Science ®], [Google Scholar]
47. Cheng PK, Wong DA, Tong LK, et al. Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome. Lancet. 2004;363(9422):1699–1700. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
48. Al-Abdely HM, Midgley CM, Alkhamis AM, et al. Middle East respiratory syndrome coronavirus infection dynamics and antibody responses among clinically diverse patients, Saudi Arabia. Emerging Infect Dis. 2019;25(4):753–766. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
49. Loeffelholz MJ, and, Tang Y-W. Laboratory diagnosis of emerging human coronavirus infections – the state of the art. Emerg Microb Infect. 2020;9:747–756. [Taylor & Francis Online], [Web of Science ®], [Google Scholar]
50. Yelin I, Aharony N, Shaer Tamar E, et al. Evaluation of COVID-19 RT-qPCR test in multi-sample pools. Clin Infect Dis. 2020. DOI:10.1093/cid/ciaa531 [Crossref], [Google Scholar]
51. Hogan CA, Sahoo MK, Pinsky BA. Sample pooling as a strategy to detect community tTransmission of SARS-CoV-2. JAMA. 2020;323(19):1967. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
52. Wyllie AL, Fournier J, Casanovas-Massana A, et al. Saliva is more sensitive for SARS-CoV-2 detection in COVID-19 patients than nasopharyngeal swabs. medRxiv. 2020. DOI:10.1101/2020.04.16.20067835 [Crossref], [Google Scholar]
53. Wu Z-S, Zhang Z-Q, Wu S. Focus on the crosstalk between COVID-19 and urogenital systems. J Urol. 2020;204(1):7–8. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
54. Guan W-J, Ni Z-Y, Hu Y, et al. Clinical characteristics of 2019 novel coronavirus infection in China. New Engl J Med. 2020;382(18):1708–1720. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
55. Notomi T, Okayama H, Masubuchi H, et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 2000;28(12):E63. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
56. Broughton JP, Deng X, Yu G, et al. CRISPR–Cas12-based detection of SARS-CoV-2. Nat Biotech. 2020. DOI:10.1038/s41587-020-0513-4 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
57. Liu Y, Yan L-M, Wan L, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis. 2020;20(6):656–657. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
58. Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Lancet. 2020. DOI:10.1093/cid/ciaa344 [Crossref], [PubMed], [Google Scholar]
59. Zhang G, Nie S, Zhang Z, et al. Longitudinal change of SARS-Cov2 antibodies in patients with COVID-19. J Infect Dis. 2020. DOI:10.1093/infdis/jiaa229 [Crossref], [Google Scholar]
60. Long Q-X, Liu B-Z, Deng H-J, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nature Med. 2020;26:845–848. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
61. Haveri A, Smura T, Kuivanen S, et al. Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February. Euro Surveill. 2020;25(11):2000266. [Crossref], [Google Scholar]
62. Amanat F, Stadlbauer D, Strohmeier S, et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat Med. 2020. DOI:10.1101/2020.03.17.20037713 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
63. Elshabrawy HA, Coughlin MM, Baker SC, et al. Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing. PLoS One. 2012;7(11):e50366. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
64. Group PIW, Multi-National P, Davey RT, Jr, et al. A randomized, controlled trial of zmapp for Ebola virus infection. N Engl J Med. 2016;375:1448–14456. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
65. Wang C, Li W, Drabek D, et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun. 2020;11(1):2251. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
66. Okba NMA, Müller MA, Li W, et al. Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease 2019 patients. Emerg Infect Dis. 2020. DOI:10.3201/eid2607.200841 [Crossref], [Web of Science ®], [Google Scholar]
67. Tang F, Quan Y, Xin ZT, et al. Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. JI. 2011;186(12):7264–7268. [Google Scholar]
68. Foundation for Innovative New Diagnostics (FIND). 2020. Available from: https://www.finddx.org/covid-19/sarscov2-eval-immuno/[Google Scholar]
69. Chan JF, Kok KH, Zhu Z, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020;9(1):221–236. [Taylor & Francis Online], [Web of Science ®], [Google Scholar]
70. An overview of the rapid test situation for COVID-19 diagnosis in the EU/EEA. Technical Report, 1 April 2020. European Centre for Disease Prevention and Control. Stockholm, 2020. Available from: https://www.ecdc.europa.eu/sites/default/files/documents/Overview-rapid-test-situation-for-COVID-19-diagnosis-EU-EEA.pdf[Google Scholar]
71. Nuccetelli M, Grelli S, Ciotti M, et al. SARS-CoV-2 infection serology: a useful tool to overcome lockdown? Cell Death Discov. 2020;6:38. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
72. Carter LJ, Garner LV, Smoot JW, et al. Assay techniques and test development for COVID-19 diagnosis. ACS Cent Sci. 2020;6(5):591–605. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
73. Huang C, Wen T, Shi F-J, et al. Rapid detection of IgM antibodies against the SARS-CoV-2 virus via colloidal gold nanoparticle-based lateral-flow assay. ACS Omega. 2020;5(21):12550–12556. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
74. Shen B, Zheng Y, Zhang X, et al. Clinical evaluation of a rapid colloidal gold immunochromatography assay for SARS-Cov-2 IgM/IgG. Am J Transl Res. 2020;12(4):1348–1354. [PubMed], [Web of Science ®], [Google Scholar]
75. Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
76. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020;5(4):562–569. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
77. Walls AC, Park YJ, Tortorici MA, et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;181(2):281–292.e6. pii: S0092-8674(20)30262-2. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
78. Shang J, Ye G, Shi K, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020;581(7807):221–224. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
79. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271–280. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
80. Wang W, Su B, Pang L, et al. High-dimensional immune profiling by mass cytometry revealed immunosuppression and dysfunction of immunity in COVID-19 patients. Cell Mol Immunol. 2020;17(6):650–652. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
81. Chu H, Zhou J, Wong BH, et al. Middle East respiratory syndrome coronavirus efficiently infects human primary T lymphocytes and activates the extrinsic and intrinsic apoptosis pathways. J Infect Dis. 2016;213(6):904–914. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
82. Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 2008;9(3):231–241. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
83. Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008;9(1):47–59. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
84. Hardwick JM, Youle RJ. SnapShot: BCL-2 proteins. Cell. 2009;138(2):404, 404.e1. [Crossref], [PubMed], [Google Scholar]
85. Wei L, Sun S, Xu CH, et al. Pathology of the thyroid in severe acute respiratory syndrome. Hum Pathol. 2007;38(1):95–102. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
86. Yeung M-L, Yao Y, Jia L, et al. MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2. Nat Microbiol. 2016;1(3):16004. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
87. Tan Y-X, Tan THP, Lee M-R, et al. Induction of apoptosis by the severe acute respiratory syndrome coronavirus 7a protein is dependent on its interaction with the Bcl-XL protein. J Virol. 2007;81(12):6346–6355. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
88. Tao X, Hill TE, Morimoto C, et al. Bilateral entry and release of Middle East respiratory syndrome coronavirus induces profound apoptosis of human bronchial epithelial cells. J Virol. 2013;87(17):9953–9958. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
89. Chen Y, Feng Z, Diao B, et al. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly decimates human spleens and lymph nodes. medRxiv. DOI:10.1101/2020.03.27.20045427 [Crossref], [Google Scholar]
90. Bordi L, Castilletti C, Falasca L, et al. Bcl-2 inhibits the caspase-dependent apoptosis induced by SARS-CoV without affecting virus replication kinetics. Arch Virol. 2006;151(2):369–377. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
91. Chan CM, Ma CW, Chan WY, et al. The SARS-coronavirus membrane protein induces apoptosis through modulating the Akt survival pathway. Arch Biochem Biophys. 2007;459(2):197–207. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
92. Khan S, Fielding BC, Tan TH, et al. Over-expression of severe acute respiratory syndrome coronavirus 3b protein induces both apoptosis and necrosis in Vero E6 cells. Virus Res. 2006;122(1–2):20–27. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
93. Schaecher SR, Touchette E, Schriewer J, et al. Severe acute respiratory syndrome coronavirus gene 7 products contribute to virus-induced apoptosis. J Virol. 2007;81(20):11054–11068. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
94. Tan YJ, Fielding BC, Goh PY, et al. Overexpression of 7a, a protein specifically encoded by the severe acute respiratory syndrome coronavirus, induces apoptosis via a caspase-dependent pathway. J Virol. 2004;78(24):14043–14047. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
95. Yuan X, Shan Y, Zhao Z, et al. G0/G1 arrest and apoptosis induced by SARS-CoV 3b protein in transfected cells. Virol J. 2005;2:66. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
96. Chan C-M, Tsoi H, Chan W-M, et al. The ion channel activity of the SARS-coronavirus 3a protein is linked to its pro-apoptotic function. Int J Biochem Cell Biol. 2009;41(11):2232–2239. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
97. Versteeg GA, Van De Nes PS, Bredenbeek PJ, et al. The coronavirus spike protein induces endoplasmic reticulum stress and upregulation of intracellular chemokine mRNA concentrations. J Virol. 2007;81(20):10981–10990. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
98. Feng S, Shen C, Xia N, et al. Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med. 2020;8(5):434–436. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
99. Chan JF, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395(10223):514–523. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
100. Zhang W, Du RH, Li B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect. 2020;9(1):386–389. [Taylor & Francis Online], [Web of Science ®], [Google Scholar]
101. Chen W, Lan Y, Yuan X, et al. Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity. Emerg Microbes Infect. 2020;9(1):469–473. [Taylor & Francis Online], [Web of Science ®], [Google Scholar]
102. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA. 2020;323(15):1488. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
103. van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. New Engl J Med. 2020;382:1564–1567. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
104. Suman R, Javaid M, Haleem A, et al. Sustainability of coronavirus on different surfaces. J Clin Exp Hepatol. 2020. DOI:10.1016/j.jceh.2020.04.020 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
105. Lippi G, Adeli K, Ferrari M, et al. Biosafety measures for preventing infection from COVID-19 in clinical laboratories: IFCC Taskforce Recommendations. [Google Scholar]
106. World Health Organization. Home care for patients with COVID-19 presenting with mild symptoms and management of their contacts. Available from: https://www.who.int/publications-detail/home-care-for-patients-with-suspected-novel-coronavirus-(ncov)-infection-presenting-with-mild-symptoms-and-management-of-contacts[Google Scholar]
107. Ahn D-G, Shin H-J, Kim M-H, et al. Current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019 (COVID-19). J Microbiol Biotechnol. 2020;30(3):313–324. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
108. Handbook of COVID-19 Prevention and Treatment. Available from: https://www.alnap.org/help-library/handbook-of-covid-19-prevention-and-treatment[Google Scholar]
109. World Health Organization. Global surveillance for COVID-19 caused by human infection with COVID-19 virus: interim guidance. Available from: https://www.who.int/publications-detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-nCov) [Google Scholar]
110. Knowles SR, Phillips EJ, Dresser L, et al. Common adverse events associated with the use of ribavirin for severe acute respiratory syndrome in Canada. Clin Infect Dis. 2003;37(8):1139–1142. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
111. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395(10236):1569–1578. [Published correction appears in Lancet. 2020;395(10238):1694. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
112. Li HS, Kuok DIT, Cheung MC, et al. Effect of interferon alpha and cyclosporine treatment separately and in combination on Middle East respiratory syndrome coronavirus (MERS-CoV) replication in a human in-vitro and ex-vivo culture model. Antiviral Res. 2018;155:89–96. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
113. Chinese clinical guidance for COVID-19 pneumonia diagnosis and treatment (7th ed). [cited 2020 May 11]. Available from: http://kjfy.meetingchina.org/msite/news/show/cn/3337.html[Google Scholar]
114. Xu CY, Lu SD, Ye X, et al. Combined treatment of tocilizumab and chloroquine on severe COVID-19: a case report. QJM. 2020. DOI:10.1093/qjmed/hcaa153 [Crossref], [Web of Science ®], [Google Scholar]
115. Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA. 2020;323(16):1582–1589. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
116. Prattes J, Valentin T, Hoenigl M, et al. Invasive pulmonary aspergillosis complicating COVID-19 in the ICU – a case report. Med Mycol Case Rep. 2020. DOI:10.1016/j.mmcr.2020.05.001 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
117. Pham DT, Toeg H, De Paulis R, et al. Establishment and management of mechanical circulatory support during the COVID-19 pandemic. Circulation. 2020. DOI:10.1161/CIRCULATIONAHA.120.047415 [Crossref], [Web of Science ®], [Google Scholar]
118. Gopalakrishnan A, Mossaid A, Lo KB, et al. Fulminant acute kidney injury in a young patient with novel coronavirus 2019. Cardiorenal Med. 2020. DOI:10.1159/000508179 [Crossref], [Web of Science ®], [Google Scholar]
119. Dastan F, Saffaei A, Mortazavi SM, et al. Continues renal replacement therapy (CRRT) with disposable hemoperfusion cartridge: a promising option for severe COVID-19. J Glob Antimicrob Resist. 2020;21:340–341. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
120. Yang XH, Sun RH, Zhao MY, et al. Expert recommendations on blood purification treatment protocol for patients with severe COVID-19: recommendation and consensus. Chronic Dis Transl Med. 2020;6(2):106-114. [Google Scholar]
121. Zhao JP, Hu Y, Du TH, et al. Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia. Chin J Tuber Respir Dis. 2020; 43:183–184. [Google Scholar]
122. Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020;7(1):4. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
123. Correa H, Malloy-Diniz LF, Da Silva AG. Why psychiatric treatment must not be neglected during the COVID-19 pandemic. Braz J Psychiatry. 2020. DOI:10.1590/1516-4446-2020-0995 [Crossref], [Google Scholar]
124. Huang YF, Bai C, He F, et al. Review on the potential action mechanisms of Chinese medicines in treating coronavirus disease 2019 (COVID-19). Pharmacol Res. 2020;158:104939. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
125. Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020;92(4):418–423. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
126. COVID-19 treatment and vaccine tracker. Available from: https://milkeninstitute.org/covid-19-tracker[Google Scholar]
127. Colson P, Rolain J-M, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020;55(3):105923. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
128. Study to ask: Does antimalarial drug prevent COVID-19? Available from: https://newsroom.uw.edu/news/does-antimalarial-drug-pre-vent-covid-19-study-seeks-answers[Google Scholar]
129. Liu T, Luo S, Libby P, et al. Cathepsin L-selective inhibitors: a potentially promising treatment for COVID-19 patients. Pharmacol Ther. 2020. DOI:10.1016/j.pharmthera.2020.107587 [Crossref], [Web of Science ®], [Google Scholar]
130. Cheng Y, Wong R, Soo YOY, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005;24(1):44–46. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
131. Accorsi P, Berti P, de Angelis V, et al. Position paper on the preparation of immune plasma to be used in the treatment of patients with COVID-19. Blood Transfus. 2020;18(3):163–166. [PubMed], [Web of Science ®], [Google Scholar]
132. World Health Organization. Infection prevention and control during health care when novel coronavirus(nCoV) infection is suspected interim guidance. [cited 2020 Jan 25]. Available from: https://apps.who.int/iris/handle/10665/330674[Google Scholar]
133. Thanh Le T, Andreadakis Z, Kumar A, et al. The COVID-19 vaccine development landscape. Nat Rev Drug Discov. 2020;19(5):305–306. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
134. China’s development of vaccines against novel coronavirus. National Health Commission of the People’s Republic of China. Available from: http://en.nhc.gov.cn/2020-03/26/c_78336.htm[Google Scholar]
135. Ahmed SF, Quadeer AA, McKay MR. Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies. Viruses. 2020;12(3):254. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
136. COVID-19 vaccine. Wikipedia. [2020 Apr 25; cited 2020 Apr 27]. Available from: https://en.wikipedia.org/w/index.php?title=COVID-19_vaccine&oldid=953116109[Google Scholar]
137. Kim E, Erdos G, Huang S, et al. Microneedle array delivered recombinant coronavirus vaccines: immunogenicity and rapid translational development. EBioMedicine. 2020;55:102743. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
138. Nunneley DCE. COVID-19 vaccine candidates: 6 front-runners. ABC News. 2020. Available from: https://abcnews.go.com/Health/covid-19-vaccine-candidates-front-runners/story?id=69881230[Google Scholar]
139. COVID-19 program vision. Available from: https://www.symvivo.com/covid-19[Google Scholar]
140. Singh S, Kumar R, Agrawal B. Adenoviral vector-based vaccines and gene therapies: current status and future prospects. London: IntechOpen; 2018. [Google Scholar]
141. Zhu FC, Li YH, Guan XH, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020;395(10240):1845–1854. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
142. Randolph HE, Barreiro LB. Herd immunity: understanding COVID-19. Immunity. 2020;52(5):737–741. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
143. Mo H, Zeng G, Ren X, et al. Longitudinal profile of antibodies against SARS-coronavirus in SARS patients and their clinical significance. Respirology. 2006;11(1):49–53. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
144. Callow KA, Parry HF, Sergeant M, et al. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect. 1990;105(2):435–446. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
145. Mashamba-Thompson TP, Crayton ED. Blockchain and artificial intelligence technology for novel coronavirus disease 2019 self-testing. Diagnostics. 2020;10(4):198. [Crossref], [Web of Science ®], [Google Scholar]
146. McCall B. COVID-19 and artificial intelligence: protecting health-care workers and curbing the spread. Lancet Digit Health. 2020;2(4):e166–e167. [Crossref], [PubMed], [Google Scholar]
147. Li L, Qin L, Xu Z, et al. Artificial intelligence distinguishes COVID-19 from community acquired pneumonia on chest CT. Radiology. 2020. DOI:10.1148/radiol.2020200905 [Crossref], [Google Scholar]
148. Rao A, Vazquez JA. Identification of COVID-19 can be quicker through artificial intelligence framework using a mobile phone-based survey in the populations when cities/towns are under quarantine. Infect Control Hosp Epidemiol. 2020;3:1–18. [Google Scholar]
149. Beck BR, Shin B, Choi Y, et al. Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model. Comput Struct Biotechnol J. 2020;18:784–790. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
150. Senior AW, Evans R, Jumper J, et al. Improved protein structure prediction using potentials from deep learning. Nature. 2020;577(7792):706–710. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
151. Rosenbaum L. Facing Covid-19 in Italy — ethics, logistics, and therapeutics on the epidemic’s front line. N Engl J Med. 2020;382(20):1873–1875. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
152. Forsman RW. Why is the laboratory an afterthought for managed care organizations? Clin Chem. 1996;42(5):813–816. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
153. Dietzen DJ. Unleashing the power of laboratory developed tests: CLOSING gaps in COVID diagnosis and beyond. J Applied Lab Med. 2020. DOI:10.1093/jalm/jfaa077 [Crossref], [Google Scholar]

Copyright © 2022 Informa UK Limited Privacy policy Cookies Terms & conditions AccessibilityRegistered in England & Wales No. 3099067
5 Howick Place | London | SW1P 1WG