Skip to content
Publicly Available Published by De Gruyter July 19, 2021

A dossier on COVID-19 chronicle

  • Rufaida , Tarique Mahmood EMAIL logo , Ismail Kedwai , Farogh Ahsan ORCID logo , Arshiya Shamim , Mohammad Shariq and Saba Parveen

Abstract

The dissemination of the 2019 novel coronavirus (2019-nCoV) is presenting the planet with a new health emergency response or threat to health. The virus emerged in bats and was disseminated to humans in December 2019 via still unknown intermediate species in Wuhan, China. It is disseminated by inhalation or breaks out with infected droplets and the incubation period is between 2 and 14 days. The symptoms usually include high body temperature, cough, sore throat, dyspnea, low energy or tiredness, and weakness. The condition is moderate in most people; but in the elderly and those with comorbidities, it advances to pneumonia, acute respiratory distress syndrome (ARDS), and multiple organ failure. Popular research work includes normal/low WBC with upraised C-reactive protein (CRP). Treatment is generally supportive and requires home seclusion of suspected persons and rigorous infection control methods at hospitals. The Covid-19 has lower fatality than SARS and MERS. Among the proposed therapeutic regimen, hydroxychloroquine, chloroquine, remdisevir, azithromycin, toclizumab, and cromostat mesylate have shown promising results, and the limited benefit was seen with lopinavir–ritonavir treatment in hospitalized adult patients with severe COVID-19. Early development of the SARS-CoV-2 vaccine started based on the full-length genome analysis of severe acute respiratory syndrome coronavirus. Several subunit vaccines, peptides, nucleic acids, plant-derived, and recombinant vaccines are under pipeline. Research work, development of new medicines and vaccines, and efforts to reduce disease morbidity and mortality must be encouraged to improve our position in the fight against this disease and to protect human life.

Introduction

The biggest challenge to public health is the current epidemic of respiratory disease that earned the name Coronavirus disease 2019 (Covid-19). In December 2019, a bunch of pneumonia cases, resulting from lately detected beta coronavirus, occurred in Wuhan, China. On February 12, the World Health Organization (WHO) described it as the 2019-novel coronavirus (2019-nCoV) that spread rapidly across the world [1], [2]. On 3 January 2020, the incident was labelled as the Public Health Emergency of International Concern (PHEIC). The fatality ratio was much lower than the SARS of 2003, but the dissemination has been substantially higher. As of November 30, 2020, the total number of Covid-19 cases was 63,083,565 with a total death of 1,465,309. India reported 94,32,129 confirmed cases as of now with 1,37,177 deaths and 88,46,475 recoveries with higher mortality and morbidity among elderly people. The fatality rate is approximately 2–3% according to the currently reported cases [3].

In response to Covid-19, many countries used a mix of confinement and prevention measures to postpone major disease outbreaks and raised hospital bed demand. Activities to achieve these objectives differ and are established on national risk evaluation that involves the approximate number of patients needing hospitalization, hospital bed availability, and ventilator support [4], [5], [6]. Most national contingencies include self isolation or quarantine; promotion of public health measures, including hand-washing, respiratory hygiene, and social distancing; readiness of health systems advent of critically ill patients needing isolation, oxygen, and mechanical ventilation; improving health facility for the prevention and control of diseases, postponing or cancelling large-scale public meetings [7], [8], [9].

This article is aimed to provide a brief review of current knowledge of the Covid-19 and summarize important clinical features as documented at present.

Origin and transmission of Covid-19

In December 2019, adults in Wuhan began to pose extreme pneumonia of unknown origin to nearby hospitals. Numerous earliest cases were usually introduced on the wholesale market for seafood, where live animals were often traded. The monitoring devices were activated and respiratory samples for etiological studies were sent to reference labs. China informed the WHO of the outbreak on December 31st, 2019, and on 1st January seafood market was closed. The virus was reported to have 95% homology to bat coronavirus and >70% similarity to SARS-CoV-2. Studies evaluated that the number of reproduction (R0) was approximately 2.2 [10] or even more (range from 1.4 to 6.5) [11], [12], which is rapidly rising through human-to-human dissemination.

During the Chinese New Year, the outbreak was fuelled by massive Chinese migration. Cases were registered in Provinces of China, and in people coming back to Wuhan from other countries [13].

Spread of Covid-19 in India

India reported its first Covid-19 case in Kerala on January 30, rising to three cases all of which were students returning from Wuhan, China. The remaining of February saw no substantial rise in incidents. On 6 March, 28 new cases were reported, including those of a group of Italian tourists with 14 members infected [14].

The dissemination intensified during March, followed by several cases across the world [15].

Confirmed cases crossed 100 on 15 March, https://en.wikipedia.org/wiki/2020_coronavirus_pandemic_in_India - cite_note-28 82,990 by 15 March, 100,000 by 15 July and 94,32,129 by 30 November with 1,37,177 deaths and 88,46,475 recoveries.

Global impact of Covid-19

At first, the assumption was that only in China would the Covid-19 be restricted. It subsequently escalated with people travelling all over the globe. The economic hardship was serious as people were compelled to stay at home, and the impact has been felt in different economic sectors with the travel ban, cancellation of sports activities, a ban on mass congregation concerning activities, and the recreation business [16].

As of November 30, 2020, the Covid-19 outbreak has been confined to around 210 countries. The virus has infected 63,083,565 people worldwide with a total death of 1,465,309. The countries worst affected include the United States, Brazil, and India.

Regional data published by the WHO on the expansion of the Covid-19 suggest that the highest number of Covid-19 cases is in Europe followed by America and Asia [17].

It is projected that the international economy could decline due to the coronavirus pandemic, the decrease could be 1%, the UN said, admonishing it can shrink even more if the economic downturn restrictions are expanded without appropriate budgetary responses.

Coronavirus structure and life process

Coronavirus is an enveloped globular or changeable particle with mono filamentous (positive sense) ribonucleic acid (RNA) and a capsid nucleoprotein consisting of a protein matrix [18], [19]. The envelope holds an expression of a glycoprotein projection formed by a club [20]. Many coronaviruses often contain a protein called esterases of hemagglutinin (HE) [21].

Coronaviruses have the genetic material (26.4–31.7 kb) of all known G + C containing RNA viruses ranging from 32 to 43%. Varying open reading frames (ORFs) between the various retained genes and downstream of the nucleocapsid gene in different lineages of coronaviruses are present. The viral genetic material includes a distinctive N-terminal inside the protein spike. For all coronavirus proteins including S, E, M, and N occur in the order 5–3′ [22], [23].

Coronavirus contains six ORFs in its genetic material. Excluding gamma coronavirus which encodes nsp1, the first ORFs (ORF1a/b), approximately two-thirds of the entire genome length encode 16 different nsps [24]. Polypeptides are transformed into 16 nsps by virally encoded protease like chymotrypsin (3CLpro) or key protease (Mpro) or proteases like papain. Both the proteins are translated of CoVs from sgRNA. Spike (S), envelope (E), nucleocapsid (N), and membrane (M) proteins are encoded on the 3′-terminus by 10, 11 ORFs. There are different proteins that CoVs encode such as 3a/b protein, HE protein, and 4a/b protein. These proteins cause genetic material preservation and replication [25].

The coronavirus is composed of 3–4 membranes of viral proteins. There is an interaction joining the envelope protein that determines the composition and formation of the membrane of the coronavirus. In the existence of tunicamycin coronavirus grows and produces spike-less, non infectious virions that do not contain S but contain M [26], [27], [28].

Entrance mechanism of human coronaviruses

Coronavirus entrance is dependent on proteases like human airway trypsin (HAT), cathepsins, and transmembrane protease serine 2 (TMPRSS2) [29].

SARS-CoV-2 spike protein contains a coronavirus structure that expresses certain polyproteins, nucleoproteins, and membrane proteins, such as RNA polymerase, 3-chymotrypsin-like protease, papain-like protease, glycoprotein, and accessory proteins [30], [31], [32], [33]. In the region of RBD, the spike protein SARS-CoV-2 holds a 3-D structure to support the forces of the Van der Waals. The residue of 394-glutamine in the SARS-CoV-2 region is identified by the residue of essential lysine 31 on the ACE2 receptor of humans [34].

SARS-CoV-2 begins its biological cycle inside the cell of the host when ACE2 receptors to S protein [35], [36]. After binding with the receptor, the S protein’s conformation changes and facilitates envelope fusion with the biological membrane with the help of the endosomal channel. SARS-CoV-2 then releases RNA into the human host cell. RNA is transformed into viral replicase polyproteins pp1a and 1ab, which are broken by viral proteinases into small fragments. The polymerase generates subgenomic mRNAs via interrupted transcription, eventually converting them into appropriate proteins. Subsequently, viral proteins and RNA gets collected in endoplasmic reticulum (ER) and Golgi virions and then carried with the help of vesicles and thrown from the cell [37], [38], [39], [40], [41], [42].

Mode of transmission of Covid-19

COVID-19 virus is transmitted between humans via minute respiratory droplets and communication paths. The occurrence of droplet transmissions takes place in a person who is in close contact (within 1 m) with someone who has respiratory symptoms (e.g., coughing or sneezing) and is thus, at the risk of exposure to potentially infectious respiratory droplets through his/her mucosae or conjunctiva. An infected individual releases fomite into the immediate environment which leads to the transmission of the virus [43], [44], [45], [46].

Another mode of transmission observed is airborne transmission which is possible particularly in situations where aerosols are generated include:

  1. Bronchoscopy

  2. Endotracheal intubation

  3. Nebulized treatment

  4. Manual ventilation preceding intubation

  5. Tracheostomy

  6. Cardiopulmonary resuscitation

  7. Patient being disconnected from the ventilator

Some research indicates that Covid-19 affects bowel movement as well, sometimes manifesting in feces as well. However, only one research till date has been able to extract the virus from a single stool specimen, on the other hand, the fecal–oral transmission of the virus has not been reported till date [47].

Human to animal transmission

The first documented case of an animal infected with COVID-19 is believed to be a tiger in the Bronx Zoo, in New York City. The National Veterinary Services Laboratory in Lowa confirmed the test result. The tiger is thought to be infected by an asymptomatic zookeeper [48].

Pathogenesis

Abnormal respiratory findings, an unusually high number of leucocytes and a raised level of proinflammatory cytokines in the plasma are traits exhibited by patients who have been diagnosed with the virus. A particular case report of a Covid-19 patient indicated that he suffered symptoms of cough, raspy breathing sound in both lungs, and a body temperature of 39 degrees Celsius. The infection was confirmed by using the sputum of the patient which yielded positive results in the real-time polymerase chain reaction. Studies conducted in the laboratory showed leukopenia with a leukocyte count of 2.91 × 109 cells/L, out of which neutrophils comprised 70%. Severe pneumonia, RNAaemia coupled with the occurrence of ground-glass opacities, and acute cardiac injury are the main pathogenesis of the respiratory system targeting virus. A Covid-19 patient has a significantly high level of cytokines and chemokines. In extreme cases, which require ventilation in the intensive care unit, high levels of proinflammatory cytokines were reasoned to encourage the severity of the disease [49], [50], [51], [52], [53].

Factors affecting virus pathogenesis

Co-morbidities include both cardiovascular and cerebrovascular disease and diabetes. A few of the other disorders observed and reported in COVID-19 patients are cellular immune deficiency, coagulation activation, myocardial injury, hepatic, and kidney injury. Most of serious illness and death cases have reported findings of lymphopenia. A point to take note of is that these findings are comparable to those suffering from SARS during the 2003 epidemic [54].

Several forms of S protein-dependent vaccines and antiviral drugs have been previously tested. Vaccines can be based on the S protein include full-length S protein, viral vector, DNA, recombinant S protein, and recombinant RBD protein. Considering that the antiviral therapies dependent on S protein are included in the in-vitro analysis as RBD–ACE2 blockers, S cleavage inhibitors, fusion core blockers, neutralizing antibodies, protease inhibitors, S protein inhibitors, and small interfering RNAs. The receptor-binding domain of SARS-CoV-2 exhibits a higher affinity for ACE2 [55], [56], [57], [58], [59].

Despite belonging to the ACE family of dipeptidylcarboxy dipeptidase, the angiotensin-converting enzyme (ACE) and its counterpart ACE2 have varied physiological functions. ACE2 acts as the COVID-19 binding site. Based on the information, the ACE2 acts as the COVID-19 binding site, Gurwitz proposed the use of accessible angiotensin receptor 1 (AT1R) blockers, to minimize the severity of COVID-19 infection with the help of a therapeutic drug such as Losartan. To understand the rate of virus spread among humans, it is essential to determine whether COVID-19 is mutating to strengthen its binding with human receptors for infection, given its rate of mutation. Any improvement in the COVID-19 series that could make it more effective for people to transmit, could also improve its virulence [60].

Diagnostic criteria

The identification of nucleic acids in the screening of nasal and throat swabs or other respiratory tract samples by polymerase chain reaction (PCR) in real-time is considered the most accurate and sought-after clinical diagnostic tool for Covid-19 [61], [62].

Complications

Complications that arise with infection are ARDS, arrhythmia, acute kidney injury, acute heart injury, liver disease, and secondary infection. The severity of the disease leads to a low clinical outcome. The elderly are adversely affected due to the quick growth of the virus in that age group [63]. On the other hand, young children also seem to be vulnerable to this virus with over 50,000 reported cases, of which the youngest was just 30 h old [64]. Therefore, the elderly and neonates require greater care and attention because of their immature or poor immune systems [65], [66], [67], [68], [69].

Treatment

As with any other virus, treatment is solely for the symptoms affecting a patient and requires respiratory support according to the diagnosis and treatment of pneumonia caused by COVID-19 and extracorporeal membrane oxygenation (ECMO) was suggested by the WHO for patients with refractory hypoxemia [70].

Currently, there is no antiviral drug or vaccine that has been approved by the WHO. The real challenge that we face is the development of an effective and reliable vaccine which ideally should be a wide-spectrum treatment. This process is a painstakingly long, combined effort of research and development. In the meantime, what we can do is systematically screen preexisting drugs to assess their activity against the Covid-19 virus.

Remdesivir, which is an antiviral drug, has been found to be successful in the treatment of a wide range of RNA viruses due to which Holshue et al. formally announced unprecedented breakthroughs in the treatment of a Covid-19 patient. After Holshue et al. [71], Xioa et al. [72] showed through their research effective in-vitro control of 2019 nCoV infection. Chloroquine has been found to have an immune-modulating function that could effectively inhibit the virus in-vitro [73]. The clinical trials have strongly shown its potential in COVID-19 patients [74], [75]. An antiparasitic drug called ivermectin has been noted to have inhibited the SARS-CoV – two from replicating in-vitro [76]. Tocilizumab is a recombinant humanized anti-human IL-6 receptor monoclonal antibody that binds to the IL-6 receptor with high affinity. An initial observational study conducted by Xu et al. [77] has shown favorable results for tocilizumab therapy [78], [79]. Convalescent plasma has been widely used to boost the endurance of patients [80], [81], [82]. Some blood centers have started assembling plasma from patients who have recovered from Covid-19, with hopes that their plasma contains antibodies that are able to resolve the virus in infected individuals. Corticosteroids, particularly methylprednisolone, have been suggested as an adjunctive agent in Covid-19 treatment. Corticosteroids have been successful in treating severe pneumonia and lung damage because of their anti-inflammatory nature [83]. Camostat mesylate is a protease inhibitor, successful against trypsin, plasmin, kallikrein, and thrombin [84], [85], [86]. It also inhibits the serine protease TMPRSS2 [87]. Based on the current understanding of the SARS-CoV-2 infection mechanism, TMPRSS2 facilitates the activation of the viral S-protein and subsequent membrane fusion and entry. This makes camostat mesylate a possible pharmacological agent to inhibit SARS-CoV-2 entry into host lung cells, averting initial infection. SARS-CoV-2 utilizes the ACE2 receptor for host cell entry, making it a potential target for COVID-19 pharmacotherapy [88]. This has invigorated debate within the scientific community, as according to some postulate blocking ACE2 receptors with ACE inhibitors and ARBs may lead to a low performance by upregulating the receptors and increasing viral entry [89]. Conflicting in vitro studies make it unclear whether these agents are therapeutic or harmful in COVID-19 patients [90] (Table 1).

Table 1:

Possible treatment of Covid-19 by using existing drug.

Drug Mechanism References
Antiviral agents
Remdesivir RNA-dependent RNA polymerase inhibitor [71, 9195]
Lopinavir, favipiravir, and ritonavir RNA-dependent RNA polymerase inhibitor [75, 96100]
Oseltamivir Neuraminidase inhibitor [83, 90, 101]
Umifenovir Spike protein/ACE2 membrane fusion inhibitor [83, 102106]
Chloroquine and hydroxychloroquine Chloroquine suppresses developing and releasing of TNF-α and IL-6 an inhibitor of autophagy that interrupts viral replication [73, 107112]
Ivermectin Unclear maybe by inhibiting IMPα/β- mediated nuclear import of viral protein. [76, 113, 114]
Immunomodulatory agents
Tocilizumab Tocilizumab is a recombinant humanized antihuman IL-6 receptor monoclonal antibody that binds to the IL-6 receptor with high affinity. [78, 79, 115118]
Interferons (ex. IFNα and IFNβ) Activate interferon-stimulated genes: Interfere with viral replication, immunomodulatory effects [106], [119], [120], [121], [122], [123], [124], [125]
Adjunctive agents
Azithromycin Antibacterial; used in combination hydroxychloroquine for synergistic antiviral effect. [126], [127], [128], [129], [130]
Corticosteroids Cytokine gene expression Inhibitor [83, 131133]
Miscellaneous agents
Camostat mesylate Serine protease inhibitor [8487, 90, 102]
ACE inhibitor/ARB ACE inhibitor; inhibit formation of angiotensin II ARB; angiotensin II receptor antagonist. [89, 134137]
  1. RNA, Ribonucleic Acid; ACE, Angiotensin Converting Enzyme; TNF, Tumor Necrosis Factor; IL, Interleukin; IMP, Importin.

Vaccines

More than 180 vaccine candidates, based on several different platforms are currently in development against SARS-CoV-2 the WHO maintains a working document [138] that includes most of the vaccines in development [139]. The platforms can be divided into ‘traditional’ approaches (inactivated or live-virus vaccines), platforms that have recently resulted in licensed vaccines (recombinant protein vaccines and vectored vaccines), and platforms that are yet to result in a licensed vaccine (RNA and DNA vaccines) [140] (Table 2).

Table 2:

COVID-19 candidate vaccine.

COVID-19 vaccine manufacturer Vaccine platform Type Clinical stage
AstraZeneca Nonreplicating viral vector ChAdOx1-S Phase III
Sinovac Inactivated Inactivated Phase III
Bharat biotech Inactivated Whole-virion Phase III
Moderna RNA Lipid nano particle (LNP)-encapsulated mRNA Phase III
Pfizer RNA 3 LNP-mRNAs Phase III
Sinopharm Inactivated Inactivated Phase III
Curevac RNA mRNA Phase III
Anhui Zhifei Protein subunit Adjuvented Phase II
Vaxart Nonreplicating viral vector Ad5 adjuvanted oral vaccine platform Phase I

Few vaccines have been authorized. Pfizer/BioNTech’s BNT162b2 received temporary authorization from the UK Medicines and Healthcare products Regulatory Agency on 2 December. Sputnik V – formerly known as Gam-COVID-Vac and developed by the Gamaleya Research Institute in Moscow – was approved by the Ministry of Health of the Russian Federation on 11 August.

Prevention

The focus of preventive measures is to optimize protocols for infection control and isolation which are clinically approved and have clinical care. Close interaction with patients, farm animals, and wildlife has all been warned against by the WHO. To avoid aerial transmission of the virus, cough and sneezes must be covered by the general public, especially in the outdoors. Regular handwashing with antiseptic soap and water is still the most effective way of prevention [141], but due to the shortage of water in densely populated urban areas hand sanitizers can be used as a preventive measure. Immune-compromised patients are strictly advised to stay indoors and avoid public gatherings. The department of emergency medicine must be given the authority to put in place strict hygiene-based initiatives to curb the spread of infection. Personal protective equipment kits [142], [143] must include N95 masks [144], [145], FFP3 masks, gowns, eye protection, gloves, and gowns [146], [147], [148], [149], [150].

Conclusion

The Covid-19 pandemic has spread all over the globe at an unprecedented pace leaving disaster in its wake. The Covid-19 pandemic presents an immense challenge globally that has been met with a remarkable response through the rapid production of pharmacological research and clinical trials. The most medically advanced countries of the world have buckled under the strain caused due by the rapid spreading of the virus glaring holes in the medical capacity of governments have been exposed such as an insufficient number of hospital beds, inadequate personal protective equipment (PPE) supply, meager morgue capacity, etc. Based on comparison with SARS or MERS the COVID-19 virus has caused more infections and a higher body count. Based on the R0 values, SARS-CoV-2 is more contagious than SARS or MERS. Immuno-compromised patients and the elderly face a greater risk of fatality compared to the rest of the population. The exact working mechanism of the virus remains a mystery and no drug has been found to completely combat the virus. Therefore, it is imperative to track down the source of infection and cut it down at its origin, cut off the transmission route, and then concentrate efforts in eliminating the virus with the help of available drugs. There is also a need to proactively monitor the progress of the disease. The duration of therapy should be individualized to the patient and the progression of the disease.

At present, management is focused on case detection, monitoring infection, prevention, and supportive care. Research work, development of new medicines and vaccines, and efforts to reduce disease morbidity and mortality must be encouraged to improve our position in the fight against this disease and to protect human life. Extensive research on therapy, possible vaccines against the virus, and its characterization as a novel virus are a result of the tireless efforts of medical researchers, professionals, academicians, and workers.


Corresponding author: Dr. Tarique Mahmood, Associate Professor & Head, Faculty of Pharmacy, Integral University, Lucknow 226026, India, Mobile: +91 9918681701, E-mail:

Acknowledgment

The author expresses her gratitude toward Hon. Chancellor, Prof. Syed Waseem Akhtar, Integral University and Vice-Chancellor (Acting), Prof. Aqil Ahmad, Integral University for providing research environment and all necessary facility for conducting research. The university has provided a communication number for further internal communication (IU/R&D/2020- MCN000936).

  1. Research funding: No funding received.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors declare that they have no competing interests.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethics approval: Not required.

  6. Consent for publication: All author’s/institution have given their consent for publication of the manuscript.

References

1. Lu, R, Zhao, X, Li, J, Niu, P, Yang, B, Wu, H, et al.. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020;395:565−74. https://doi.org/10.1016/s0140-6736(20)30251-8.Search in Google Scholar

2. Li, Q, Guan, X, Wu, P, Wang, X, Zhou, L, Tong, Y, et al.. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020;382:1199−207. https://doi.org/10.1056/nejmoa2001316.Search in Google Scholar

3. Rinaldi, G, Paradisi, M. An empirical estimate of the infection fatality rate of COVID-19. Medrxiv 2020:20070912.10.1101/2020.04.18.20070912Search in Google Scholar

4. Wang, X, Pan, Z, Cheng, Z. Association between 2019-nCoV transmission and N95 respirator use. J Hosp Infect 2020;5:104–5. https://doi.org/10.1016/j.jhin.2020.02.021.Search in Google Scholar

5. Kwok, YL, Gralton, J, McLaws, ML. Face touching: a frequent habit that has implications for hand hygiene. Am J Infect Contr 2015;43:112–4. https://doi.org/10.1016/j.ajic.2014.10.015.Search in Google Scholar

6. Eikenberry, SE, Mancuso, M, Iboi, E, Phan, T, Eikenberry, K, Kuang, Y. To mask or not to mask: modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic. Infect Dis Model 2020;5:293−308. https://doi.org/10.1016/j.idm.2020.04.001.Search in Google Scholar

7. Bedford, J, Enria, D, Giesecke, J, Heymann, D. COVID-19: towards controlling of a pandemic. Lancet 2020;395:1015−8. https://doi.org/10.1016/s0140-6736(20)30673-5.Search in Google Scholar

8. Zhang, L, Shen, M, Ma, X, Su, S, Gong, W, Wang, J, et al.. What is required to prevent a second major outbreak of SARS-CoV-2 upon lifting the quarantine of Wuhan city, China. Innovation 2020;1:100006. https://doi.org/10.1016/j.xinn.2020.04.006.Search in Google Scholar PubMed PubMed Central

9. Shen, M, Peng, Z, Guo, Y, Rong, L, Li, Y, Xiao, Y, et al.. Assessing the effects of metropolitan-wide quarantine on the spread of COVID-19 in public space and households. Int J Infect Dis 2020;96:503−5. https://doi.org/10.1016/j.ijid.2020.05.019.Search in Google Scholar PubMed PubMed Central

10. Riou, J, Althaus, L. Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January. Euro Surveill 2020;25:2000058. https://doi.org/10.2807/1560-7917.es.2020.25.4.2000058.Search in Google Scholar PubMed PubMed Central

11. Liu, Y, Gayle, AA, Wilder-Smith, A, Rocklöv, J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Trav Med 2020;27:taaa021.10.1093/jtm/taaa021Search in Google Scholar

12. Chan, JW, Yuan, S, Kok, KH, To, W, Chu, H, Yang, J, 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;395:5145−23. https://doi.org/10.1016/S0140-6736(20)30154-9.Search in Google Scholar

13. Rothe, C, Schunk, M, Sothmann, P, Bretzel, G, Froeschl, G, Wallrauch, C, et al.. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med 2020;382:970–1. https://doi.org/10.1056/nejmc2001468.Search in Google Scholar

14. Coronavirus: India defiant as millions struggle under lockdown. BBC; 2020. Available from: https://www.bbc.com/news/world–asia–india–52077395 [Accessed 30 May 2020].Search in Google Scholar

15. Six members of Delhi patient’s family test positive for coronavirus. The Hindu; 2020. Available from: https://thehindu.com/news/cities/Delhi/covid–19–6–members–of–delhi–patients–family–test–positive–for–coronavirus/article30980724.ece [Accessed 15 April 2020].Search in Google Scholar

16. The global coronavirus recession is beginning. CNN; 2020. Available from: https://edition.cnn.com/2020/03/16/economy/global–recessioncoronavirus/index.html [Accessed 10 April 2020].Search in Google Scholar

17. WHO. Coronavirus disease 2019 (COVID-19): situation report; 2020. Available from: https://www.who.int/docs/default–source/coronaviruse/situation–reports/20200515–sitrep115covid19.pdf?sfvrsn=2791b4e0_2.opensinnewtab [Accessed 20 May 2020].Search in Google Scholar

18. Gorbalenya, EA, Baker, ES, Baric, SR, Groot, R, Drosten, C. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 2020;5:536–44. https://doi.org/10.1038/s41564-020-0695-z.Search in Google Scholar

19. Corman, VM, Muth, D, Niemeyer, D, Drosten, C. Hosts and sources of endemic human coronaviruses. Adv Virus Res 2018;100:163–88. https://doi.org/10.1016/bs.aivir.2018.01.001.Search in Google Scholar

20. Gorbalenya, AE, Enjuanes, L, Ziebuhr, J, Snijder, EJ. Nidovirales: evolving the largest RNA virus genome. Virus Res 2006;117:17–37. https://doi.org/10.1016/j.virusres.2006.01.017.Search in Google Scholar

21. Lei, J, Li, J, Li, X, Qi, X. CT imaging of the 2019 novel coronavirus (2019-nCoV) pneumonia. Radiology 2020;295:18.10.1148/radiol.2020200236Search in Google Scholar

22. Perlman, S, Netland, J. Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol 2009;7:4394−50. https://doi.org/10.1038/nrmicro2147.Search in Google Scholar

23. Masters, PS. The molecular biology of coronaviruses. Adv Virus Res 2006;65:193–292. https://doi.org/10.1016/s0065-3527(06)66005-3.Search in Google Scholar

24. Liu, DX, Fung, TS, Chong, KL, Shukla, A, Hilgenfeld, R. Accessory proteins of SARS-CoV and other coronaviruses. Antivir Res 2014;109:97−109. https://doi.org/10.1016/j.antiviral.2014.06.013.Search in Google Scholar PubMed PubMed Central

25. Huang, C, Wang, Y, Li, X, Ren, L, Zhao, J, Hu, Y, et al.. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497−506. https://doi.org/10.1016/s0140-6736(20)30183-5.Search in Google Scholar

26. Haan, CA, Kuo, L, Masters, PS, Vennema, H, Rottier, PJ. Coronavirus particle assembly: primary structure requirements of the membrane protein. J Virol 1998;72:6838−50. https://doi.org/10.1128/jvi.72.8.6838-6850.1998.Search in Google Scholar

27. Schalk, A, Hawn, MC. An apparently new respiratory disease of baby chicks. J Am Vet Med Assoc 2020;78:413−23.Search in Google Scholar

28. Hamre, D, Procknow, JJ. A new virus isolated from the human respiratory tract. Proc Soc Exp Biol Med 1966;121:190−3. https://doi.org/10.3181/00379727-121-30734.Search in Google Scholar

29. Woo, PC, Huang, Y, Lau, SK, Yuen, KY. Coronavirus genomics and bioinformatics analysis. Viruses 2010;2:1804−20. https://doi.org/10.3390/v2081803.Search in Google Scholar

30. Li, Q, Med, M, Guan, X, Wu, P, Wang, X. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020;382:1199−207. https://doi.org/10.1056/nejmoa2001316.Search in Google Scholar

31. Dai, H Fa, Yuan, L, P Yuan, W Fan. A new coronavirus associated with human respiratory disease in China. Nature 2020;579:565−9.Search in Google Scholar

32. Lee, N. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003;348:1986−94. https://doi.org/10.1056/nejmoa030685.Search in Google Scholar

33. Peiris, JM. SARS study group, Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 2003;361:1319–25. https://doi.org/10.1016/s0140-6736(03)13077-2.Search in Google Scholar

34. Czub, M, Weingartl, H, Czub, S, He, R, Cao, J. Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets. Vaccine 2003;23:2273−9. https://doi.org/10.1016/j.vaccine.2005.01.033.Search in Google Scholar PubMed PubMed Central

35. Chu, H. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clin Infect Dis 2020;71:1400–9. https://doi.org/10.1093/cid/ciaa410.Search in Google Scholar PubMed PubMed Central

36. Li, F. Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol 2016;3:2372−61. https://doi.org/10.1146/annurev-virology-110615-042301.Search in Google Scholar PubMed PubMed Central

37. Bertram, S, Glowacka, I, Müller, MA, Lavender, H, Gnirss, K, Nehlmeier, I, et al.. Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease. J Virol 2011;85:13363−72. https://doi.org/10.1128/jvi.05300-11.Search in Google Scholar

38. Shang, J, Ye, G, Li, F. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020;581:221−4. https://doi.org/10.1038/s41586-020-2179-y.Search in Google Scholar PubMed PubMed Central

39. Walls, C. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020;181:281–92.e6. https://doi.org/10.1016/j.cell.2020.02.058.Search in Google Scholar PubMed PubMed Central

40. Wrapp, D. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020;367:1260–3. https://doi.org/10.1126/science.abb2507.Search in Google Scholar PubMed PubMed Central

41. Hoffmann, M. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271–80.e8. https://doi.org/10.1016/j.cell.2020.02.052.Search in Google Scholar PubMed PubMed Central

42. Ou, X, Liu, Y, Qian, Z. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 2020;11:1620. https://doi.org/10.1038/s41467-020-15562-9.Search in Google Scholar PubMed PubMed Central

43. Wu, F, Zhao, S, Yu, B, Chen, YM, Wany, W, Song, ZG, et al.. A new coronavirus associated with human respiratory disease in China. Nature 2020;579:265−9. https://doi.org/10.1038/s41586-020-2008-3.Search in Google Scholar PubMed PubMed Central

44. Liu, T, Hu, J, Xiao, J, He, G, Kang, M, Rong, Z. Time-varying transmission dynamics of Novel coronavirus pneumonia in China. bioRxiv 2020;3:250–9.10.1101/2020.01.25.919787Search in Google Scholar

45. Klok, FA, Kruip, MA, Meer, NJM, Arbous, MS, Gommers, J, Kant, KM, et al.. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020;191:145−7. https://doi.org/10.1016/j.thromres.2020.04.013.Search in Google Scholar PubMed PubMed Central

46. Tian, N, Hu, J, Lou, K, Chen, X, Kang, Z. Characteristics of COVID-19 infection in Beijing. J Infect 2020;80:4014−06. https://doi.org/10.1016/j.jinf.2020.02.018.Search in Google Scholar PubMed PubMed Central

47. Raj, VS, Mou, H, Smits, SL, Dekkers, DH, Müller, MA, Dijkman, R, et al.. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013;495:251−4. https://doi.org/10.1038/nature12005.Search in Google Scholar

48. Daly, N. Seven more big cats test positive for coronavirus Bronx Zoo; 2020. National Geographic coronavirus coverage 2020 May 5. Available from: http://www.natgeotraveller.in/tiger–tests–positive–for–coronavirus–at–bronx–zoo/ [Accessed 17 May 2020].Search in Google Scholar

49. Xu, X, Chen, P, Wang, J, Feng, J, Zhou, H, Li, X, et al.. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci 2020;63:457−60. https://doi.org/10.1007/s11427-020-1637-5.Search in Google Scholar

50. Sia, SF, Yan, LM, Chin, AWH. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature 2020;583:834−8. https://doi.org/10.1038/s41586-020-2342-5.Search in Google Scholar

51. Monteil, V, Kwon, H, Prado, P. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020;181:9059−13. https://doi.org/10.1016/j.cell.2020.04.004.Search in Google Scholar

52. Varga, Z, Flammer, AJ, Steiger, P. Endothelial cell infection and endotheliosis in COVID-19. Lancet 2020;395:14178−8. https://doi.org/10.1016/S0140-6736(20)30937-5.Search in Google Scholar

53. Mangalmurti, N, Hunter, CA. Cytokine storms: understanding COVID-19. Immunity 2020;53:192−5. https://doi.org/10.1016/j.immuni.2020.06.017.Search in Google Scholar

54. Ouassou, H, Kharchoufa, L, Bouhrim, M. The pathogenesis of coronavirus disease 2019 (COVID-19): evaluation and prevention. J Immunol Res 2020;2020:1357983. https://doi.org/10.1155/2020/1357983.Search in Google Scholar

55. Yang, X, Yu, Y, Xu, J, Shu, H, Liu, H, Wu, Y, et al.. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020;8:475−81. https://doi.org/10.1016/s2213-2600(20)30079-5.Search in Google Scholar

56. Takahashi, T, Ellingson, MK, Wong, P. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020;4:178–87. https://doi.org/10.1038/s41586-020-2700-3.Search in Google Scholar

57. Liu, Y, Yan, LM, Wan, L. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020;20:656−7. https://doi.org/10.1016/s1473-3099(20)30232-2.Search in Google Scholar

58. Baez-Santos, YM, Mesecar, AD. The SARS coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds. Antivir Res 2015;115:21−38. https://doi.org/10.1016/j.antiviral.2014.12.015.Search in Google Scholar

59. Lucas, C, Wong, P, Klein, J. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020;584:463−9. https://doi.org/10.1038/s41586-020-2588-y.Search in Google Scholar

60. Liu, C, Zhou, Q, Albaiu, D. Research and development on therapeutic agents and vaccines for Covid-19 and related human coronavirus diseases. ACS Cent Sci 2020;6:315−31. https://doi.org/10.1021/acscentsci.0c00272.Search in Google Scholar

61. Muharraqi, M. Testing recommendation for COVID-19 (SARS-CoV-2) in patients planned for surgery-continuing the service and ‘suppressing’ the pandemic. Br J Oral Maxillofac Surg 2020;58:503−5. https://doi.org/10.1016/j.bjoms.2020.04.014.Search in Google Scholar

62. Patel, E, Babady, ES, Theel, GA, Storch, BA, Pinsky, KS. Report from the American Society for Microbiology COVID-19 international summit, 23 march 2020: value of diagnostic testing for SARS–CoV-2/COVID-19. Am Soc Microbiol 2020;11:e00722–20. https://doi.org/10.1128/mBio.00722-20.Search in Google Scholar

63. Gurwitz, D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutic. Drug Dev Res 2020;2:14−9. https://doi.org/10.1002/ddr.21656.Search in Google Scholar

64. Wang, J, Qi, H, Bao, L, Li, F, Shi, Y. A contingency plan for the management of the 2019 novel coronavirus outbreak in neonatal intensive care units. Lancet Child Adolesc Health 2020;4:258−9. https://doi.org/10.1016/s2352-4642(20)30040-7.Search in Google Scholar

65. Promislow, DE. A geroscience perspective on COVID-19 mortality. J Gerontol A Biol Sci Med Sci 2020;75:e30–3. https://doi.org/10.1093/gerona/glaa094.Search in Google Scholar PubMed PubMed Central

66. Rémi, CD, Guern, C, Tinez, A, Laurent, R, Sophie, S. Panton-valentine leukocidin-secreting staphylococcus aureus pneumonia complicating COVID-19. Emerg Infect Dis 2020;26:1939−42.10.3201/eid2608.201413Search in Google Scholar PubMed PubMed Central

67. Kluge, U, Janssens, T, Welte, S, WebeCarstens, Marx, G, Karagiannidis, C. German recommendations for critically ill patients with COVID-19. Med Klin Intensivmed Notfallmed 2020;115:111–4.10.1007/s00063-020-00689-wSearch in Google Scholar PubMed PubMed Central

68. Xiaochen, L, Shuyun, X, Muqing, Y, Wang, K, Tao, U, Ying, Z. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol 2020;146:110−8. https://doi.org/10.1016/j.jaci.2020.04.006.Search in Google Scholar PubMed PubMed Central

69. Ullah, W, Saeed, R, Sarwar, U, Patel, R, Fischman, DL. COVID-19 complicated by acute pulmonary embolism and right-sided heart failure. JACC Case Report 2020;2:1379−82. https://doi.org/10.1016/j.jaccas.2020.04.008.Search in Google Scholar PubMed PubMed Central

70. WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected; 2020. Available from: https://www.who.int/publicationsdetail/clinical–management–of–severe–acute–respiratory–infection–when–novelcoronavirus–(ncov)–infection–is–suspected [Accessed 30 March 2020].Search in Google Scholar

71. Holshue, ML, DeBolt, C, Lindquist, S, Lofy, KH, Wiesman, J, Bruce, H, et al.. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020;382:929−36. https://doi.org/10.1056/nejmoa2001191.Search in Google Scholar

72. Xioa, X, Ge, H, Wang, X. The epidemiology and clinical information about COVID-19. Eur J Clin Microbiol 2020;14:1−9. https://doi.org/10.1007/s10096-020-03874-z.Search in Google Scholar PubMed PubMed Central

73. Wang, M, Cao, R, Zhang, L, Yang, X, Liu, J, Xu, M, et al.. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269–71. https://doi.org/10.1038/s41422-020-0282-0.Search in Google Scholar PubMed PubMed Central

74. J Gao, Tian, Z, Yang, X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of Covid-19 associated pneumonia in clinical studies. Biosci Trends 2020;14:727−31. https://doi.org/10.5582/bst.2020.01047.Search in Google Scholar PubMed

75. Cao, B, Wang, Y, Wen, D, Liu, WS. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020;382:1787−99. https://doi.org/10.1056/nejmoa2001282.Search in Google Scholar PubMed PubMed Central

76. Leon, C, Julian, D, Catton, M, Jans, D. The FDA approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antivir Res 2020;178:104787.10.1016/j.antiviral.2020.104787Search in Google Scholar PubMed PubMed Central

77. Xu, X, Han, M, Li, T, Sun, W, Wang, D, Fu, B, et al.. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci 2020;117:1–12. https://doi.org/10.1073/pnas.2005615117.Search in Google Scholar PubMed PubMed Central

78. Luo, P, Liu, Y, Qiu, L, Liu, X, Liu, D, Li, J. Tocilizumab treatment in COVID-19: a single centre experience. J Med Virol 2020;97:814–8. https://doi.org/10.1002/jmv.25801.Search in Google Scholar PubMed PubMed Central

79. Zhang, C, Wu, Z, Li, JW, Zhao, H, Wang, GQ. The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality. Int J Antimicrob Agents 2020;55:105954. https://doi.org/10.1016/j.ijantimicag.2020.105954.Search in Google Scholar

80. Rajendran, K, Narayanasamy, K, Rangarajan, J, Rathinam, J, Natarajan, M, Ramachandran, A. Convalescent plasma transfusion for the treatment of COVID-19: systematic review. J Med Virol 2020;92:1475–83. https://doi.org/10.1002/jmv.25961.Search in Google Scholar

81. Rojas, M, Rodríguez, Y, Monsalve, DM, Acosta-Ampudia, Y, Camacho, B, Gallo, JE, et al.. Convalescent plasma in Covid-19: possible mechanisms of action. Autoimmun Rev 2020;9:102554. https://doi.org/10.1016/j.autrev.2020.102554.Search in Google Scholar

82. Zhao, Q, He, Y. Challenges of convalescent plasma therapy on COVID-19. J Clin Virol 2020;127:104358. https://doi.org/10.1016/j.jcv.2020.104358.Search in Google Scholar

83. Yousefi, B, Valizadeh, S, Ghaffari, H, Vahedi, A, Karbalaei, M, Eslami, M. A global treatment for coronaviruses including COVID-19. J Cell Physiol 2020;11:10–1002. https://doi.org/10.1002/jcp.29785.Search in Google Scholar

84. Coote, K, Watson, HC, Sugar, R, Young, A, MacKenzie-Beevor, A, Gosling, M, et al.. Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease. J Pharmacol Exp Therapeut 2009;329:764–74. https://doi.org/10.1124/jpet.108.148155.Search in Google Scholar

85. Bittmann, S. Covid 19: camostat and the role of serine protease entry inhibitor TMPRSS2. J Regen Biol Med 2009;2:020.10.37191/Mapsci-2582-385X-2(2)-020Search in Google Scholar

86. Hoffmann, M, Kleine-Weber, H, Schroeder, S, Krüger, N, Herrler, T, Erichsen, S, et al.. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271–80. https://doi.org/10.1016/j.cell.2020.02.052.Search in Google Scholar PubMed PubMed Central

87. Uno, Y. Camostat mesilate therapy for COVID-19. Intern Emerg Med 2020;15:1577–8. https://doi.org/10.1007/s11739-020-02345-9.Search in Google Scholar PubMed PubMed Central

88. McLachlan, SV. The angiotensin converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms. J Clin Hypertens 2020;26:14. https://doi.org/10.1186/s40885-020-00147-x.Search in Google Scholar PubMed PubMed Central

89. Esler, M, Esler, D. Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? J Hypertens 2020;38:781–2. https://doi.org/10.1097/hjh.0000000000002450.Search in Google Scholar PubMed

90. Sanders, JM, Monogue, ML, Jodlowski, TZ, Cutrell, JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. J Am Med Assoc 2020;12;323:1824−36. https://doi.org/10.1001/jama.2020.6019.Search in Google Scholar PubMed

91. Elfiky, AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci 2020;28:117477. https://doi.org/10.1016/j.lfs.2020.117477.Search in Google Scholar PubMed PubMed Central

92. Tawfiq, JA, Homoud, AH, Memish, ZA. Remdesivir as a possible therapeutic option for the COVID-19. Trav Med Infect Dis 2020;34:101615. https://doi.org/10.1016/j.tmaid.2020.101615.Search in Google Scholar PubMed PubMed Central

93. Yethindra, V. Role of GS-5734 (Remdesivir) in inhibiting SARS-CoV and MERS-CoV: the expected role of GS-5734 (Remdesivir) in COVID-19 (2019-nCoV)-VYTR hypothesis. Int J Res Pharm Sci 2020;6:1–6. https://doi.org/10.26452/ijrps.v11ispl1.1973.Search in Google Scholar

94. Ko, WC, Rolain, JM, Lee, NY, Chen, PL, Huang, CT, Lee, PI, et al.. Arguments in favour of remdesivir for treating SARS-CoV-2 infections. Int J Antimicrob Agents 2020;55:105933. https://doi.org/10.1016/j.ijantimicag.2020.105933.Search in Google Scholar PubMed PubMed Central

95. Sheahan, TP, Sims, AC, Leist, SR, Schäfer, A, Won, J, Brown, AJ, et al.. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon-beta against MERS-CoV. Nat Commun 2020;11:222–9. https://doi.org/10.1038/s41467-019-13940-6.Search in Google Scholar PubMed PubMed Central

96. Chu, CM, Cheng, VC, Hung, IF, Wong, MML, Chan, KH, Chan, KS, et al.. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004;59:252–60. https://doi.org/10.1136/thorax.2003.012658.Search in Google Scholar PubMed PubMed Central

97. Huang, J, Song, W, Huang, H, Sun, Q. Pharmacological therapeutics targeting RNA-dependent RNA polymerase, proteinase and spike protein: from mechanistic studies to clinical trials for COVID-19. J Clin Med 2020;9:1131. https://doi.org/10.3390/jcm9041131.Search in Google Scholar PubMed PubMed Central

98. Jin, Z, Du, X, Xu, Y, Deng, Y, Liu, M, Zhao, Y, et al.. Structure of Mpro from COVID-19 virus and discovery of its inhibitors. bioRxiv 2020;582:289−93. https://doi.org/10.1038/s41586-020-2223-y.Search in Google Scholar PubMed

99. Vafaei, S, Razmi, M, Mansoori, M, Asadi-Lari, M, Madjd, Z. Spotlight of remdesivir in comparison with ribavirin, favipiravir, oseltamivir and umifenovir in coronavirus disease 2019 (COVID-19) pandemic. Favipiravir, Oseltamivir Umifenovir Coronavirus Disease 2019;1:39–48.10.2139/ssrn.3569866Search in Google Scholar

100. Qingxian, C, Yang, M, Liu, D, Chen, J, Shu, D, Xia, J, et al.. Experimental treatment with Favipiravir for COVID-19: an open-label control study. Engineering 2020;6:1192−8. https://doi.org/10.1016/j.eng.2020.03.007.Search in Google Scholar PubMed PubMed Central

101. Olsson, L, Alphonse, N, Dickenson, RE, Durbin, JE, Glenn, JS, Hartmann, R, et al.. COVID-19 and emerging viral infections: the case for interferon lambda. J Exp Med 2020;4:217. https://doi.org/10.1084/jem.20200653.Search in Google Scholar PubMed PubMed Central

102. A new antiviral drug heading into clinical trials offers hope for COVID-19 treatment – in part because it can be taken as a pill. Emery University; 2020. Available from: https://news.emory.edu/stories/2020/04/covid_eidd_2801_lung/index.html [Accessed 28 May 2020].Search in Google Scholar

103. Sheahan, TP, Sims, AC, Zhou, S, Graham, RL, Pruijssers, AJ, Agostini, ML, et al.. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 and multiple endemics, epidemic and bat coronavirus. Biorxiv 2020;12: eabb5883. https://doi.org/10.1126/scitranslmed.abb5883.Search in Google Scholar PubMed PubMed Central

104. Khamitov, RA, SIa, L, Shchukina, VN, Borisevich, SV, Maksimov, VA, Shuster, AM. Antiviral activity of arbidol and its derivatives against the pathogen of severe acute respiratory syndrome in the cell cultures. Vopr Virusol 2008;53:9–13.Search in Google Scholar

105. Yousefifard, M, Zali, A, Ali, KM, Neishaboori, AM, Zarghi, A, Hosseini, M, et al.. Antiviral therapy in management of COVID-19: a systematic review on current evidence. Arch Acad Emerg Med 2020;8:e45–54.10.1111/ijcp.13557Search in Google Scholar PubMed PubMed Central

106. Chan, JW, Chan, KH, Kao, RT, To, KW, Zheng, BJ, Li, CY, et al.. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Infect Dis 2013;67:606–16. https://doi.org/10.1016/j.jinf.2013.09.029.Search in Google Scholar PubMed PubMed Central

107. Ohe, M, Shida, H, Jodo, S, Kusunoki, Y, Seki, M, Furuya, K, et al.. Macrolide treatment for COVID-19: will this be the way forward? Biosci Trends 2020;14:159−60. https://doi.org/10.5582/bst.2020.03058.Search in Google Scholar PubMed

108. Dahly, D, Gates, S, Morris, T. Statistical review of hydroxychloroquine and azithromycin as a treatment of COVID19: results of an open-label nonrandomized clinical trial. Preprint. Posted online 2020;23:33–7.Search in Google Scholar

109. Lane, JC, Weaver, J, Kostka, K, Duarte-Salles, T, Abrahao, MT, Alghoul, H, et al.. Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study. medRxiv 2020;5:452–61.Search in Google Scholar

110. Gabriels, J, Saleh, M, Chang, D, Epstein, LM. Inpatient use of mobile continuous telemetry for COVID-19 patients treated with hydroxychloroquine and azithromycin. HeartRhythm Case Reports 2020;6:241–3. https://doi.org/10.1016/j.hrcr.2020.03.017.Search in Google Scholar PubMed PubMed Central

111. Gautret, P, Lagier, J, Parola, P, Hoang, VT, Meddeb, L, Mailhe, M, et al.. Hydroxychloroquine and azithromycin as a treatment of COVID19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020;56:105949. https://doi.org/10.1016/j.ijantimicag.2020.105949.Search in Google Scholar PubMed PubMed Central

112. Guzik, T, Mohiddin, SA, Dimarco, A, Patel, V, Savvatis, K, Marelli-Berg, FM. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res 2020;116:1666–87. https://doi.org/10.1093/cvr/cvaa106.Search in Google Scholar PubMed PubMed Central

113. Wagstaff, KM, Sivakumaran, H, Heaton, SM, Harrich, D, Jans, DA. Ivermectin is a specific inhibitor of importin alpha/beta169 mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J 2012;443:851–6. https://doi.org/10.1042/bj20120150.Search in Google Scholar

114. Patrì, A, Fabbrocini, G. Hydroxychloroquine and ivermectin: a synergistic combination for COVID-19 chemoprophylaxis and/or treatment? J Am Acad Dermatol 2020;82:e221–9. https://doi.org/10.1016/j.jaad.2020.04.017.Search in Google Scholar PubMed PubMed Central

115. Wu, R, Wang, L, Kuo, HCD, Shannar, A, Peter, R, Chou, PJ et al.. An update on current therapeutic drugs treating COVID-19. Curr Pharmacol 2020;11:11−5. https://doi.org/10.1007/s40495-020-00216-7.Search in Google Scholar PubMed PubMed Central

116. Xu, X, Han, M, Li, T, Sun, W, Wang, D, Fu, B, et al.. Effective treatment of severe COVID-19 patients with tocilizumab. ChinaXiv 2020;117:1–12. https://doi.org/10.1073/pnas.2005615117.Search in Google Scholar PubMed PubMed Central

117. Van, FL, Veerdonk, DM, de Graaf, LA, Joosten, CA. Biology of IL-38 and its role in disease. Immunol Rev 2018;281:191–6. https://doi.org/10.1111/imr.12612.Search in Google Scholar PubMed

118. Salvi, R, Patankar, P. Emerging pharmacotherapies for COVID-19. Biomed Pharmacother 2020;128:110267. https://doi.org/10.1016/j.biopha.2020.110267.Search in Google Scholar PubMed PubMed Central

119. Belhadi, D, Peiffer-Smadja, N, Yazdanpanah, Y, Mentr´e, F, Laou´enan, C. A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19. medRxiv 2020;2:65–74.10.1101/2020.03.18.20038190Search in Google Scholar

120. Martinez, MA. Compounds with therapeutic potential against novel respiratory 2019 coronavirus. Antimicrob Agents Chemother 2020;64:e00399–408. https://doi.org/10.1128/AAC.00399-20.Search in Google Scholar PubMed PubMed Central

121. Sallard, E, Lescure, FX, Yazdanpanah, Y, Mentre, F, Peiffer-Smadja, N. Type 1 interferons as a potential treatment against COVID-19. Antivir Res 2020;178:104791. https://doi.org/10.1016/j.antiviral.2020.104791.Search in Google Scholar PubMed PubMed Central

122. Arabi, YM, Alothman, A, Balkhy, HH, Dawood, A, Johani, S, Harbi, M, et al.. Treatment of Middle East Respiratory Syndrome with a combination of lopinavirritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials 2018;19:81–92. https://doi.org/10.1186/s13063-017-2427-0.Search in Google Scholar PubMed PubMed Central

123. Kadam, RU, Wilson, IA. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol. Proc Natl Acad Sci USA 2017;114:206214. https://doi.org/10.1073/pnas.1617020114.Search in Google Scholar

124. Dong, L, Hu, S, Gao, J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther 2020;14:58–60. https://doi.org/10.5582/ddt.2020.01012.Search in Google Scholar

125. Rosenberg, ES, Dufort, EM, Udo, T, Wilberschied, LA, Kumar, J, Tesoriero, J, et al.. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York state. J Am Med Assoc 2020;323:2493−502. https://doi.org/10.1001/jama.2020.8630.Search in Google Scholar

126. Magagnoli, J, Narendran, S, Pereira, F, Cummings, T, Hardin, JW, Sutton, SS, et al.. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv 2020;1:114–27. https://doi.org/10.1016/j.medj.2020.06.001.Search in Google Scholar

127. Asensio, E, Acunzo, R, Uribe, W, Saad, EB, Saenz, LC. Recommendations for the measurement of the QT interval during the use of drugs for COVID-19 infection treatment. Updatable in accordance with the availability of new evidence. J Intervent Card Electrophysiol 2020;59:315−20. https://doi.org/10.1007/s10840-020-00765-3.Search in Google Scholar

128. Bhimraj, A, Morgan, RL, Shumaker, AH, Lavergne, V, Baden, L, Cheng, B, et al.. Infectious diseases society of America guidelines on the treatment and management of patients with COVID-19. Clin Infect Dis 2020;1:114–27. https://doi.org/10.1093/cid/ciaa478.Search in Google Scholar

129. Mehra, MR, Desai, SS, Ruschitzka, F, Patel, AN. Retraction-Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet 2020;395:1820. https://doi.org/10.1016/s0140-6736(20)31324-6.Search in Google Scholar

130. Menachery, VD, Yount, BL, Josset, L, Gralinski, LE, Scobey, T, Agnihothram, S, et al.. Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2’-O-methyltransferase activities. J Virol 2020;88:4251−64. https://doi.org/10.1128/JVI.03571-13.Search in Google Scholar PubMed PubMed Central

131. Russell, B, Moss, C, Rigg, A, Hemelrijck, M. COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting? Ecancermedicalscience 2020;14:1023. https://doi.org/10.3332/ecancer.2020.1023.Search in Google Scholar PubMed PubMed Central

132. Yang, Z, Zhou, LJ, Zhao, X, Zhao, Q, Jing, L. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J Infect 2020;81:e13–20. https://doi.org/10.1016/j.jinf.2020.03.062.Search in Google Scholar PubMed PubMed Central

133. Liu, Y, Tian, D, Wang, C, Wang, S, Cheng, J, Hu, M, et al.. Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia. Signal Transduct Target Ther 2020;5:18. https://doi.org/10.1038/s41392-020-0127-9.Search in Google Scholar PubMed PubMed Central

134. Gurwitz, D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res 2020;81:537–40. https://doi.org/10.1002/ddr.21656.Search in Google Scholar PubMed PubMed Central

135. Sriram, K, Insel, PA. Risks of ACE inhibitor and ARB usage in COVID-19: evaluating the evidence. Clin Pharmacol Ther Cpt 2020;108:236−41. https://doi.org/10.1002/cpt.1863.Search in Google Scholar PubMed PubMed Central

136. Kreutz, R, Algharably, EA, Azizi, M, Dobrowolski, P, Guzik, T, Januszewicz, A, et al.. Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19European Society of Hypertension COVID-19 Task Force Review of Evidence. Cardiovasc Res 2020;116:1688–99. https://doi.org/10.1093/cvr/cvaa097.Search in Google Scholar PubMed PubMed Central

137. McKee, DL, Sternberg, A, Stange, U, Laufer, S, Naujokat, C. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol Res 2020;157:104859. https://doi.org/10.1016/j.phrs.2020.104859.Search in Google Scholar PubMed PubMed Central

138. WHO. Draft landscape of COVID-19 candidate vaccines; 2020. Available from: https://www.who.int/publications/m/item/draft–landscape–of–covid–19–candidate–vaccines [Accessed 26 September 2020].Search in Google Scholar

139. Wang, H. Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. Cell 2020;182:713–21. https://doi.org/10.1016/j.cell.2020.06.008.Search in Google Scholar PubMed PubMed Central

140. WHO. Draft landscape of COVID-19 candidate vaccines; 2020. Available from: https://www.who.int/publications/m/item/draft–landscape–of–covid–19–candidate–vaccines [Accessed 30 November 2020].Search in Google Scholar

141. Direzione, GD. FAQ—Covid-19, Domande e Risposte. Marzo. Articolo Pubblicato su Governo.it; 2020. Available from: http://www.salute.gov.it/portale/malattieInfettive/dettaglioFaqMalattieInfettive.jsp?lingua=italiano&id=228 [Accessed 15 May 2020].Search in Google Scholar

142. Norm EN 374 2016. Available from: https://www.uni3servizi.it/2019/07/23/en–iso–374–1–2016/ [Accessed 3 July 2020].Search in Google Scholar

143. Casanova, LM, Teal, LJ, Sickbert, EE, Anderson, DJ, Sexton, DJ, Rutala, WA, et al.. Program T.C.P.E. Assessment of self-contamination during removal of personal protective equipment for ebola patient care. Infect Control Hosp Epidemiol 2016;37:1156–61. https://doi.org/10.1017/ice.2016.169.Search in Google Scholar PubMed

144. Shiu, EY, Leung, L, Cowling, BJ, Tada, H, Nohara, A, Kawashiri, MA. Controversy around airborne versus droplet transmission of respiratory viruses. Curr Opin Infect Dis 2019;32:372–9. https://doi.org/10.1097/qco.0000000000000563.Search in Google Scholar PubMed

145. Lee, SA, Grinshpun, SA, Reponen, T. Respiratory performance offered by N95 respirators and surgical masks: human subject evaluation with NaCl aerosol representing bacterial and viral particle size range. Ann Occup Hyg 2008;52:177–85. https://doi.org/10.1093/annhyg/men005.Search in Google Scholar PubMed PubMed Central

146. Chellamani, KP, Veerasubramanian, D, Balaji, V. Surgical face masks: manufacturing methods and classification. J Acad Ind Res 2013;2:6−11.Search in Google Scholar

147. Booth, CM, Clayton, M, Crook, B, Gawn, J. Effectiveness of surgical masks against influenza bioaerosols. J Hosp Infect 2013;84:22–6. https://doi.org/10.1016/j.jhin.2013.02.007.Search in Google Scholar PubMed

148. Sande, B, Teunis, P, Sabel, R. Professional and home-made face masks reduce exposure to respiratory infections among the general population. PLoS ONE 2008;3:22–3. https://doi.org/10.1371/journal.pone.0002618.Search in Google Scholar PubMed PubMed Central

149. Huang, S. COVID-19: why we should all wear masks—there is new sciencific rational; 2020. Available from: https://medium.com/@Cancerwarrior/covid–19–why–we–should–all–wear–masks–there–isnew–scientific–rationale–280e08ceee71 [Accessed 10 March 2020].Search in Google Scholar

150. Cascella, M, Rajnik, M, Cuomo, A, Dulebohn, SC, Napoli, RD. Features, evaluation and treatment coronavirus (COVID-19). Treasure Island 2020;117:6771−6.Search in Google Scholar

Received: 2020-12-15
Accepted: 2021-06-28
Published Online: 2021-07-19

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 29.3.2024 from https://www.degruyter.com/document/doi/10.1515/jbcpp-2020-0511/html
Scroll to top button