A Review of the 2019 Novel Coronavirus (COVID-19) Pandemic
B. V. Naresh*
Doctor of Pharmacy, University College of Pharmaceutical Sciences, Andhra University,
Visakhapatnam-530003, Andhra Pradesh, India.
*Corresponding Author E-mail: dr.naresh119@gmail.com
ABSTRACT:
Corona viruses are a large family of viruses which may cause illness in animals or humans. In humans, several coronaviruses are known to cause respiratory infections ranging from the common cold to more severe diseases such as Middle east respiratory syndrome (MERS) and Severe acute respiratory syndrome (SARS). The most recently discovered was coronavirus disease COVID-19 also known as Severe acute respiratory syndrome-2(SARS COV-2). In a short span, it has captured global consciousness by significantly affecting the day-to-day life of human beings. Currently, as a global pandemic, COVID-19 poses major challenges. It is a respiratory illness that can spread from person to person that was first identified in Wuhan, China. The World Health Organization has declared this as a Public health emergency of International Concern. Based on the current published evidence, this article summarizes the epidemiology, clinical features, diagnosis, treatment, vaccines and prevention COVID-19. This review is in the hope of helping the public and health care professionals effectively recognize and deal with this disease, and providing a reference for future studies.
KEYWORDS: Severe acute respiratory syndrome-2; SARS-CoV-2; COVID-19; coronavirus; global pandemic.
INTRODUCTION:
Corona viruses are a large family of viruses which may cause illness in animals or humans. In humans, several coronaviruses are known to cause respiratory infections ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The most recently discovered was coronavirus disease COVID-19.1 It is a respiratory illness that can spread from person to person that was first identified during an investigation into an outbreak in Wuhan, China.2 The World Health Organization has declared this as a Public Health Emergency of International Concern. As of now, this virus has been spread to over 207 countries around the world with a total of 1,878,489 confirmed cases and 119,044 deaths.
This posed a great threat to global public health. This article reviews the Epidemiology, reproductive number, mode of transmission, mother to fetal transmission of virus, survival on the surfaces, clinical characteristics, diagnosis, pathogenesis, pharmacological and plasma convalescent treatment and vaccines and prevention of the SARS-CoV-2, so that it can provide references for follow-up research, and may help readers to have the latest understanding of this new infectious disease.
Epidemiology:
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Aka Covid-19 has, as on April 15, 2020, spread to over 207 countries around the world with a total of 1,878,489 confirmed cases and 119,044 deaths and the number of reported SARS-CoV-2 cases in India is also on an increase with 10,363 cases and 339 deaths.3 The union health ministry of India on April 4, 2020 confirmed that around 9% of Covid-19 cases belong to 0-20 years age group, while nearly 42% are from 21-40 years age group, 33% cases between 41-60years, 17% cases are above 60 years.
Reproductive number (R0):
Reproductive number or spreadability factor is an mathematical number that indicates how contagious an infectious disease is. R0 is dependent on the exponential growth rate of an outbreak, as well as additional factors such as the latent period (the time from infection to infectiousness) and the infectious period.4,5 Initial estimates of the early dynamics of the outbreak in wuhan, china, suggested a R0 of 2.2-2.7 but the Recent Data shows that median R0 value is approximately 5.76
Mode of transmission:
Human-to-human
transmissions have been described with incubation times between 2-10 days,
facilitating its spread via droplets, contaminated hands or surfaces.17 Respiratory
infections can be transmitted through droplets of different sizes: when the
droplet particles are >5-10 μm in diameter they are referred to as
respiratory droplets, and when they are <5μm in diameter, they are
referred to as droplet nuclei.7
According to current evidence, COVID-19 virus is primarily transmitted between people through respiratory droplets and contact routes.8-13 these droplets land on objects and surfaces around the person when a infected person coughs or exhales, other people then catch COVID-19 by touching these objects or surfaces, then touching their eyes, nose or mouth. Droplet transmission occurs when a person is in close contact (within 1m) with someone who has respiratory Clinical features like coughing or sneezing.
Transmission may also occur through fomites in the immediate environment around the infected person.14 Therefore, transmission of the COVID-19 virus can occur by direct contact with infected people and indirect contact with surfaces in the immediate environment or with objects used on the infected person like stethoscope or thermometer.
Then comes
airborne transmission which is different from droplet transmission as it refers
to the presence of microbes within droplet nuclei, which are <5μm in
diameter, can remain in the air for long periods of time and be transmitted to
others over distances greater than 1 m.15
In the context of
COVID-19, airborne transmission may be possible in specific circumstances and
settings in which procedures or support treatments that generate aerosols are
performed; i.e., endotracheal intubation, bronchoscopy, open suctioning,
administration of nebulized treatment, manual ventilation before intubation,
turning the patient to the prone position, disconnecting the patient from the
ventilator, non-invasive positive-pressure ventilation, tracheostomy, and
cardiopulmonary resuscitation.15
Mother to fetal transmission of
SARS-COV-2:
Previous epidemics of many emerging viral infections
have typically resulted in poor obstetrical outcomes including maternal
morbidity and mortality, maternal-fetal transmission of the virus, and
perinatal infections and death.
A study analyzed outcomes of a total of 38
pregnant women reported with COVID-19 in China. All women were in the 3rd
trimester of pregnancy, and included 37 women whose SARS-CoV-2 positivity was
confirmed by Rt-PCR, these pregnancies resulted in 39 infants (one set of
twins); detailed clinical information, obstetrical outcomes and SARS-CoV-2
status were available for 30 neonates.In these none of them did not lead to maternal deaths.
Importantly, and similar to pregnancies with SARS (severe acute respiratory
syndrome) and MERS (middle east respiratory syndrome), there were no confirmed
cases of intrauterine transmission of SARS-CoV-2 from mothers with COVID-19 to
their fetuses. All neonatal specimens tested, were negative by Rt-PCR for
SARS-CoV-2.19
Another study which was retrospectively analyzed the
outcomes of 10 neonates (including 2 twins) born to 9 mothers with confirmed
Covid-19 infection in 5 hospitals in Hubei from January 20 to February 5, 2020.
Pharyngeal swab specimens were collected from 9 of the 10 neonates 1 to 9 days
after birth for nucleic acid amplification tests for Covid-19, all of which
showed negative results.20
At this point in the global pandemic of COVID-19 infection
there is no evidence that SARS-CoV-2 undergoes intrauterine or transplacental
transmission from infected pregnant women to their fetuses.19
Survival on the surfaces:
As per the latest
data available, SARS-CoV-2 remained viable in aerosols upto 3hours, with a
reduction in infectious titer from 103.5 to 102.7 TCID50 per liter of air. It
was more stable on plastic and stainless steel than on copper and cardboard,
and viable virus was detected up to 72 hours after application to these
surfaces, although the virus titer was greatly reduced (from 103.7 to 100.6
TCID50 per milliliter of medium after 72 hours on plastic and from 103.7 to
100.6 TCID50 per milliliter after 48 hours on stainless steel). On copper, no
viable SARS-CoV-2 was measured after 4 hours. On cardboard, no viable
SARS-CoV-2 was measured after 24 hours.16
Hence, Surface
disinfection with 0.1% sodium hypochlorite or 62% to 71% ethanol significantly
reduces coronavirus infectivity on surfaces within 1 min exposure time.17 and
it is highly necessary that one should not touch their T Zone in order to
prevent this virus entering into the body because on an average a person
touches his face 23 times per hour.18
Clinical features of COVID-19:
Reported illnesses have ranged from mild symptoms to severe illness in coronavirus disease 2019 (COVID-19) cases, these symptoms may appear 2-14 days after exposure (based on the incubation period of MERS-CoV viruses).21
Common symptoms at onset of illness were fever (98% of the patients), cough (76%), and myalgia or fatigue (44%); less common symptoms observed were sputum production (28%), headache (8%), haemoptysis (5%), and diarrhoea (3%). Dyspnoea developed in 55% of patients (median time from illness onset to dyspnoea is 8.0 days). 63% of patients had lymphopenia and Complications includes acute respiratory distress syndrome and Pneumonia. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.22
There is new evidence for the loss of smell as a symptom of COVID-19 infection. Post-viral anosmia is one of the leading causes of loss of sense of smell in adults, accounting for up to 40% cases of anosmia.23
Diagnosis of COVID-19:
Rapid and accurate detection of COVID-19 is crucial to control outbreaks in the community and in hospitals25. Current diagnostic tests for coronavirus include reverse-transcription polymerase chain reaction (RT-PCR), real‐time RT-PCR (rRT‐PCR), and reverse transcription loop‐mediated isothermal amplification (RT‐LAMP).26, 27
But the current laboratory test (RT-PCR) is time-consuming, and a shortage of commercial kits delays diagnosis. Hence for the patients suffering from fever, sore throat, fatigue, coughing or dyspnea that is coupled with recent exposure, COVID-19 infection can be diagnosed with typical chest computerized tomography (CT) characteristics despite negative RT-PCR results and the typical CT findings includes bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and peripheral lung distribution.28 In a recent study out of 1014 patients, 59% had positive RT-PCR results, and 88% had positive chest CT scans29 and there is also another way that we can reduce the time consumption of RT-PCR test was pool testing or block testing method.
During this method, if 10 samples are mixed and tested for Covid-19 and if they test negative, then it will be an indicator that all samples are negative. But if the test is not negative, then individual testing will be done. this will increase the testing capacity as well as in boosting the process to detect the virus with no decrease in sensitivity.33 there are also other tests like antibody tests that are gaining recognition as they can detect the immune response to the disease quickly. The sensitivity of RNA testing, antibody and combinational testing’s includes 67.1%, 93.1% and 99.4 % respectively.34
Hence, combinational assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia30,31,32.
Pathogenesis of SARS-COV-2:
Coronavirus (COV) is a single strand RNA virus with a diameter of 80-120nm. It is divided into four types: α-coronavirus (α-COV), β-coronavirus (β-COV), δ-coronavirus (δ-COV) and γ - coronavirus (γ-COV).35 Six coronaviruses were previously known to cause disease in humans, SARS-CoV-2 is the seventh member of the coronavirus family that infects human beings after SARS-CoV and MERS-CoV.36
Several studies revealed that SARS-CoV-2 uses angiotension-converting enzyme 2 (ACE2) as receptor, just like as SARS-CoV.37 This virus recognizes the corresponding receptor on the target cell through the S protein on its surface and enters into the cell, then causing the infection. A structure model analysis shows that SARS-CoV-2 binds ACE2 with above 10 folds higher affinity than SARS-CoV.38
The main pathogenesis of COVID-19 infection was severe pneumonia, ARDS (Acute respiratory distress syndrome), RNAaemia, combined with the incidence of ground-glass opacities, and acute cardiac injury. Increased capillary permeability is the hallmark of ARDS. Damage of the capillary endothelium and alveolar epithelium in correlation to impaired fluid removal from the alveolar space results in accumulation of protein-rich fluid inside the alveoli, and thereby producing diffuse alveolar damage, with release of pro-inflammatory cytokines like Tumor Necrosis Factor (TNF), IL-1 and IL-6.39 Neutrophils are then recruited into the lungs by cytokines, and becomes activated and releases toxic mediators, such as reactive oxygen species and proteases.39 Extensive free radical production overwhelms endogenous anti-oxidants and causes oxidative cell damage.39
Significantly high blood levels of cytokines (Cytokine storm) and chemokines were also noted in patients with COVID-19 infection that included IL1-β, IL1RA, IL7, IL8, IL9, IL10, basic FGF2, GCSF, GMCSF, IFNγ, IP10, MCP1, MIP1α, MIP1β, PDGFB, TNFα, and VEGFA. Some of the severe cases that were admitted to the intensive care unit showed high levels of pro-inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1α, and TNFα that are reasoned to promote disease severity.11
Pharmacological Treatment:
As the COVID-19 pandemic continues to spread across the world, killing thousands, the doctors, researchers and governments across the world are on the lookout for safe and effective drugs. Some of the drugs under investigations include Remdesivir, Lopinavir/ritonavir, Chloroquine and hydroxychloroquine, Tocilizumab etc.
Antiviral drugs administered shortly after symptom onset can reduce infectiousness to others by reducing viral shedding in the respiratory secretions of patients (SARS-CoV-2 viral load in sputum peaks at around 5–6 days after symptom onset and lasts up to 14 days), and targeted prophylactic treatment of contacts could reduce their risk of becoming infected.40
The antimalarial drug, hydroxychloroquine, is licensed for the chemoprophylaxis and treatment of malaria and as a disease modifying antirheumatic drug (DMARD) which is safe and well tolerated at typical doses. Notably, the drug shows antiviral activity in vitro against coronaviruses, and specifically, SARS-CoV-2.41
The Indian National Taskforce for COVID-19 recommends the use of hydroxy-chloroquine for prophylaxis of SARS-CoV-2 infection in India for Asymptomatic healthcare workers involved in the care of suspected or confirmed cases of COVID-19 as 400 mg twice a day on Day 1, followed by 400 mg once weekly for next 7 weeks; to be taken with meals and for Asymptomatic household contacts of laboratory confirmed cases as 400 mg twice a day on Day 1, followed by 400 mg once weekly for next 3 weeks; to be taken with meals. And it is also said that the drug is not recommended for prophylaxis in children under 15 years of age and it is contraindicated in persons with known case of retinopathy, known hypersensitivity to hydroxychloroquine, 4-aminoquinoline compounds.42
Remdesivir is a broad spectrum anti-viral medication (RNA dependent RNA polymerase inhibitor) developed for treatment of Ebola and also showed success in treatment of monkeys infected with MERS, a different type of coronavirus. It is now being tested as a potential COVID-19 treatment (as of now, it is being tested in clinical trials in usa and china).43
Lopinavir/ritonavir is the drug
combination used against viruses like HIV. this has also been shown to be
effective against SARS-CoV-2 in laboratory cells as well as in mice and is
being tested alongside an antiviral drug called interferon beta which is now
currently used to treat Multiple sclerosis and can enhance the natural defences
of the body’s cells against COVID-19.44 A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection
underwent randomized, controlled, open-label trial; in those 99 were assigned
to the lopinavir–ritonavir group, and 100 to the standard-care group. The study
concluded that in hospitalized adult patients with severe Covid-19, No benefit
was observed with lopinavir–ritonavir treatment beyond standard care.45
Tocilizumab (TCZ)
is a monoclonal antibody which acts against interleukin-6 (IL-6), emerged as an
alternative treatment for COVID-19 patients with a risk of cytokine storms. In
china, a single centered study on 15 Covid-19 patients shown that TCZ appears
to be an effective treatment option in COVID-19 patients with a risk of
cytokine storms.46
Vaccines:
The genetic sequence of SARS-CoV-2 was published on 11 January 2020, triggering intense global Research and development activity to develop a vaccine against the disease. As of 8 April 2020, the global COVID-19 vaccine R&D activity included 115 vaccine candidates, of which 78 are confirmed as active and 37 are unconfirmed. Numerous other vaccine developers have indicated plans to initiate human testing in 2020.47
Of the 78 confirmed active projects, 73 are currently at exploratory or preclinical stages. The most advanced candidates have recently moved into clinical development, such as mRNA-1273 from Moderna (entered into Phase-I), Ad5-nCoV from CanSino Biologicals9 (entered into Phase-II), INO-4800 from Inovio (entered into Phase-I), LV-SMENP-DC (entered into Phase-I)and pathogen-specific aAPC from Shenzhen Geno-Immune Medical Institute (entered into Phase-I).47,48
Table 1: aAPC, artificial antigen-presenting cell; CTL, cytotoxic T lymphocyte; DC, dendritic cell; LNP, lipid nanoparticle; S protein, SARS-CoV-2 spike protein.
|
Candidate |
Vaccine characteristics |
|
mRNA-1273 |
LNP-encapsulated mRNA vaccine
encoding S protein |
|
Ad5-nCoV |
Adenovirus type 5 vector that
expresses S protein |
|
INO-4800 |
DNA plasmid encoding S protein
delivered by electroporation |
|
LV-SMENP-DC |
DCs modified with lentiviral
vector expressing synthetic minigene based on domains of selected viral
proteins; administered with antigen-specific CTLs |
|
Pathogen-specific aAPC |
aAPCs modified with lentiviral
vector expressing synthetic minigene based on domains of selected viral
proteins |
Source: ClinicalTrials.gov website; WHO.
Convalescent plasma therapy:
When attacked by a pathogen, our immune systems produce proteins called antibodies to fight against the infection. If the infected person can produce sufficient antibodies, he can recover from the disease caused by that pathogen. The idea behind convalescent plasma therapy is that such immunity can be transferred from a healthy person to a sick using blood plasma to treat their disease. When there are no sufficient vaccines and specific drugs, convalescent plasma therapy could be an effective way to alleviate the course of disease for severely infected patients.49 This treatment involves injecting the COVID-19 patient with convalescent sera of people who recovered from the infection recently. This is also known as Passive antibody therapy.50
In a retrospective analysis, convalescent plasma therapy showed more effectiveness than severe doses of hormonal shock in patients with severe SARS, thereby reducing mortality and duration of hospital stays.51 Therefore, the plasma of some patients recovered from COVID-19 can be collected to prepare plasma globulin specific to SARS-CoV-2. However, the safety of such plasma globulin products deserves further evaluation.
Preventive measures:
To prevent infection and to slow transmission of COVID-19, following are some of the measures:
1. Washing hands regularly with soap and water, or cleaning them with alcohol-based hand rub.
2. Maintaining at least 1meter distance between you and people coughing or sneezing.
3. Avoid touching your face (at T zone).
4. Covering mouth and nose when coughing or sneezing.
5. Staying in home if feels unwell.
6. Refrain from smoking and other activities that weaken the lungs.
7. Practice physical distancing by avoiding unnecessary travel and staying away from large groups of people.
There also some studies that have shown that vitamin C may prevent the susceptibility of lower respiratory tract infection under certain conditions.53 Vitamin-C also known as ascorbic acid, it is a water-soluble vitamin that neutralizes a variety of reactive oxygen species and can recycle cellular anti oxidants. These levels can drop in patients with acute respiratory infection, while COVID-19 may cause lower respiratory tract infection. Therefore, a moderate amount of vitamin C supplementation may be a way to prevent COVID-19.
REFERENCES:
1. Indian Ministry of health and family welfare, accessed 15-march-2020
2. https://www.cdc.gov/coronavirus/2019-ncov/index.html, accessed 15-march-2020
3. World Health Organization. Coronavirus disease (COVID-2019) situation reports.WHO; 2020. Available from: https://www.who.int/emergencies/diseases/novelcoronavirus-2019/situation-reports, accessed on April 15, 2020.
4. Wearing HJ, Rohani P, Keeling MJ. Appropriate models for the management of infectious diseases. PLoS Med. 2005;2: e174.
5. Lloyd AL. The dependence of viral parameter estimates on the assumed viral life cycle: limitations of studies of viral load data. Proc Biol Sci. 2001; 268:847–54.
6. Sanche S, et al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020 Jul [date cited]. Available from: URL: https://doi.org/10.3201/ eid2607.200282
7. World Health Organization. Infection prevention and control of epidemic- and pandemic-prone acute respiratory infections in health care. Geneva: World Health Organization; 2014 Available from: https://apps.who.int/iris/bitstream/handle/10665/112656/ 9789241507134_eng.pdf?sequence=1
8.
Liu J, et al. Community transmission of severe acute respiratory
syndrome coronavirus 2, Shenzhen, China, 2020. Emerg Infect Dis. Available
from: 2020 doi.org/10.3201/eid2606.200239
9.
Chan 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 doi: 10.1016/S0140-6736(20)30154-9
10. Li Q, et al.
Early transmission dynamics in Wuhan, China, of novel coronavirus-infected
pneumonia. N Engl J Med 2020; doi:10.1056/NEJMoa2001316.
11. Huang C, et al.
Clinical features of patients infected with 2019 novel coronavirus in Wuhan,
China. Lancet 2020; 395: 497–506.
12. Burke RM, et al.
Active monitoring of persons exposed to patients with confirmed COVID-19 —
United States, January–February 2020. MMWR Morb Mortal Wkly Rep. 2020 doi:
10.15585/mmwr.mm6909e1external icon
13. World Health
Organization. Report of the WHO-China Joint Mission on Coronavirus Disease 2019
(COVID-19) 16-24 February 2020 [Internet]. Geneva: World Health Organization;
2020 Available from: https://www.who.int/docs/default- source/
coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf
14. Ong SW, et al.
Air, surface environmental, and personal protective equipment contamination by
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a symptomatic
patient. JAMA.2020 Mar 4
15. Mode of
transmission of virus. Available from: https:// www.who.int/news-room/commentaries/detail/modes-of-transmission-of-virus-causing-covid-19-implications-for-ipc-precaution-recommendations
16. Dr. van Doremalen,et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1 N Engl J Med 2020; 382:1564-1567 DOI: 10.1056/NEJMc2004973
17. G. Kampf et al. / Journal of Hospital Infection 104 (2020) 246e251
18. Y.L.A. Kwok et al. Face touching: a frequent habit that has implications for hand hygiene. / American Journal of Infection Control 43 (2015) 112-4
19. David A. Schwartz (2020) An Analysis of 38 Pregnant Women with COVID-19, Their Newborn Infants, and Maternal-Fetal Transmission of SARS-CoV-2: Maternal Coronavirus Infections and Pregnancy Outcomes. Archives of Pathology and Laboratory Medicine In-Press. Available from: URL: https://doi.org/10.5858/arpa.2020-0901-SA
20. Huaping Zhu, et al. Transl Pediatr 2020;9(1):51-60 | Available from: http://dx.doi.org/10.21037/tp.2020.02.06
21. Symptoms of corona virus, Available from: https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html
22. Chaolin Huang, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China www.thelancet.com Vol 395 February 15, 2020 https://doi.org/10.1016/ S0140-6736(20)30183-5
23. Loss of sense of smell as marker of COVID-19 infection Available from: www.entuk.org
24. Some corona virus patients show signs of stroke, seizures. Available from: https://www.nytimes.com/2020/04/01/health/ coronavirus-stroke-seizures-confusion.html
25. k.k., Tsang O.T., et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis. 2020
26. Bhadra S., et al. Real-time sequence-validated loop-mediated isothermal amplification assays for detection of Middle East respiratory syndrome coronavirus (MERS-CoV) PLoS One. 2015;10
27. Chan J.F., Choi G.K., Tsang A.K., Tee K.M., Lam H.Y., Yip C.C. Development and evaluation of novel real-time reverse transcription-PCR Assays with locked nucleic acid probes targeting leader sequences of human-pathogenic Coronaviruses. J Clin Microbiol. 2015; 53:2722–2726.
28. Xie X., et al. Chest CT for typical 2019-nCoV pneumonia: relationship to negative RT-PCR testing. Radiology. 2020
29. Ai T., et al. Correlation of chest CT and RT-PCR testing in Coronavirus disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology. 2020
30. Shi H., et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020; 20:425–434
31. Xu X., et al. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2. Eur J Nucl Med Mol Imaging. 2020; 47:1275–1280.
32. Wang Y., et al. Combination of RT-qPCR testing and clinical features for diagnosis of COVID-19 facilitates management of SARS-CoV-2 outbreak. J Med Virol. 2020
33. Pool testing of SARS-CoV-02 samples increases worldwide test capacities many times over/ aktuelles.uni-frankfurt.de/englisch/ pool-testing-of-sars-cov-02-samples-increases-worldwide-test-capacities-many-times-over/
34. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019 published in Clinical Infectious Diseases, ciaa344, available from: https://doi.org/10.1093/ cid/ciaa344
35. Chan JF, et al. Interspecies transmission and emergence of novel viruses: lessons from bats and birds. Trends Microbiol. 2013; 21:544-55
36. Zhu N, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. The New England journal of medicine. 2020
37. Hoffmann M, et al. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. bioRxiv. 2020:2020.01.31.929042.
38. Wrapp D, et al. Cryo-EM structure of the 2019-nCoV spike in the perfusion conformation. Science (New York, NY). 2020.
39. Charalampos Pierrakos, et al. Acute Respiratory Distress Syndrome: Pathophysiology and Therapeutic Options J Clin Med Res 2011; 4(1):7-16
40. Welliver R, et al. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA 2001; 285: 748–54
41. Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020; published online March 9. DOI:10.1093/cid/ciaa237
42. 42)Hydroxychloroquine usage recommendations by ICMR Available from: https://icmr.nic.in/sites/default/files/ upload_documents/HCQ_Recommendation_22March_final_MM_V2.pdf
43. Existing drugs that may be repurposed to treat coronavirus. Available from: https://www.nbcnews.com/health/health-news/ here-are-some-existing-drugs-may-be-repurposed-treat-coronavirus-n1162021
44. Coronavirus treatment. Available from: https:// theconversation.com/coronavirus-treatments-what-drugs-might-work-against-covid-19-135352
45. B. Cao, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19, n engl j med march 18, 2020 DOI: 10.1056/NEJMoa2001282
46. Luo P, et al. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020 Apr 6. doi: 10.1002/jmv.25801
47. The covid-19 vaccine development landscape, available from: https://www.nature.com/articles/d41573-020-00073-5
48. ad5-ncov vaccine moves into phase ii clinical-trials, available from: https://www.trialsitenews.com/chinas-covid-19-vaccine-called-ad5-ncov-moves-into-phase-ii-clinical-trial-500-volunteers-sought/
49. Mair-Jenkins J, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the
50. treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015; 211:80-90.
51. convalescent-plasma-therapy-for-covid-19. Available from: https://www.thehindu.com/scitech/health/convalescent-plasma-therapy-for-covid-19/article31371149.ece
52. Soo YO, et al. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect. 2004; 10:676-8
53. Preventive measures for Covid-19 https://www.who.int/health-topics/coronavirus#tab=tab_1
54. Hemila H. Vitamin C intake and susceptibility to pneumonia. Pediatr Infect Dis J. 1997; 16:836-7.
Received on 20.04.2020 Modified on 05.05.2020
Accepted on 29.05.2020 ©Asian Pharma Press All Right Reserved
Asian J. Pharm. Res. 2020; 10(3):233-238.
DOI: 10.5958/2231-5691.2020.00040.4