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| REVIEW ARTICLE |
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| Year : 2020 | Volume
: 18
| Issue : 2 | Page : 83-86 |
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COVID-19 – A replay of the 1918 pandemic?
Govind Sreekumar, Aparna Lohanathan, Darpanarayan Hazra
Department of Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India
| Date of Submission | 17-Mar-2020 |
| Date of Decision | 18-Mar-2020 |
| Date of Acceptance | 31-Mar-2020 |
| Date of Web Publication | 17-Apr-2020 |
Correspondence Address:
Dr. Govind Sreekumar
Department of Emergency Medicine, Christian Medical College, Vellore - 632 004, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/cmi.cmi_36_20
COVID-19 outbreak is likely to have started from a zoonotic transmission event associated with a large seafood market that also traded in live wild animals. Initial epidemiological studies suggested a predilection for older adult males with comorbidities due to their immunocompromised status and very rarely, coinfection with bacteria and fungi. An exponential increase in the number of nonlinked cases in the late December 2019 pointed toward the risk of human-to-human transmission. Similar to its predecessor, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) also acts on the angiotensin-converting enzyme-2 (ACE2) present on the type 1 and type 2 alveolar epithelial cells. ACE2 expression has been found to be higher in males than females and in Asian populations compared to White and African-American populations. This led to an agreement that the Asian males were more susceptible to SARS-CoV-2 infection. The ability of SARS-CoV-2 to bind to ACE2 receptor was found to be 10–20 times more than that of the SARS-CoV, thus making the new pathogen much more aggressive. At the time of writing this article, the global burden of confirmed cases of COVID-19 has risen to half a million with death toll touching 25,000 people. For the first time, we may be looking at a pandemic which could be controlled on a short-term basis and prevented on a long term with adequate research and clinical trials for newer therapeutic agents.
Keywords: Coronavirus, COVID-19, pandemic
How to cite this article:
Sreekumar G, Lohanathan A, Hazra D. COVID-19 – A replay of the 1918 pandemic?. Curr Med Issues 2020;18:83-6 |
| Introduction | |  |
More than a century ago, when the world refused to believe that anything of a graver consequence could befall them than the casualties of theFirst World War, the “Spanish flu” spread across the globe, prostrating millions of individuals with pneumonia, fatal enough to wipe out more than 50 million from the face of the earth.[1] The War had warranted a world that was highly mobile and interconnected, and this pandemic was the price to be paid. A 100 years later, the emergence of another deadly pathogen has the world on its toes, creating mass hysteria and boundaries among alarmed populations.
Coronaviruses, belonging to the subfamily Coronavirinae of the family Coronaviridae, were considered to be largely innocuous pathogens, causing self-limiting respiratory and intestinal illnesses in immunocompetent adults, till a severe acute respiratory distress syndrome (SARS) epidemic affected the Guangdong Province of China in the early 2003.[2] The pathogen which was isolated was named the SARS-coronavirus (CoV), and the transmission was thought to occur through market civets with the virus originating in bats. A decade later, another outbreak was noted in the Middle Eastern countries, where a similar virus was isolated from patients manifesting with a syndrome, very closely resembling the SARS-CoV in Guangdong.[3] It was named the Middle East respiratory syndrome (MERS)-CoV and was a reminder that zoonotic coronavirus infections posed a persistent threat of pandemics in this highly vascularized and interconnected world.
The late 2019 outbreak was initially called the novel coronavirus pneumonia or the Wuhan pneumonia, before being named as COVID-19 by the World Health Organization (WHO) on February 11, 2020. An epidemiological and etiological investigation commissioned by the authorities on an outbreak of pneumonia in Wuhan, Hubei Province, China, led to the isolation of a positive-sense, RNA-stranded virus which bore similarities to the Betacoronavirus found in bats and to the 2003 SARS-CoV. It was named the SARS-CoV-2.[4]
| Epidemiology | | |
The COVID-19 outbreak is likely to have started from a zoonotic transmission event associated with a large seafood market that also traded in live wild animals. However, an exponential increase in the number of nonlinked cases in the late December pointed toward the risk of human-to-human transmission.[5] Initial epidemiological studies suggested a predilection for older adult males with comorbidities due to their immunocompromised status and very rarely, coinfection with bacteria and fungi.[6] The greater affinity of SARS-CoV-2 to the upper respiratory tract with tendency to replicate in the prodromal state in a healthy carrier poses a challenge different from the 2003 Guangdong outbreak where the symptoms were more abrupt in onset and the rate of transmission during the healthy carrier state was much lower. This leads to a faster spread of the infection and makes the outbreak difficult to contain.[7],[8] After the preliminary analysis of data, the exponential spread of the infection has been taken into consideration and the mean basic reproduction number was found to be ranging from 2.24 (95% confidence interval [CI]: 1.96–2.55) to 3.58 (95% CI: 2.89–4.39).[9] In other words, on an average, each patient transmits the infection to an additional 2.2–3.6 individuals.
At the time of writing the article, the global burden of confirmed cases of COVID-19 has risen to half a million with death toll touching 25,000 people.
| Pathogenesis and Clinical Features | | |
Similar to its predecessor, SARS-CoV-2 also acts on the angiotensin-converting enzyme-2 (ACE2) present on the type 1 and type 2 alveolar epithelial cells. ACE2 expression has been found to be higher in males than females and in Asian populations compared to Caucasean and African-American populations. This led to an agreement that the Asian males were more susceptible to SARS-CoV-2 infection. The ability of SARS-CoV-2 to bind to ACE2 receptor was found to be 10–20 times more than that of the SARS-CoV, thus making the new pathogen much more aggressive.[10] Backer et al. calculated the mean incubation period to be 6.4 days (95% CI: 5.6–7.7), with incubation periods ranging from 2.1 to 11.1 days.[11] Fever is the most consistent clinical feature, followed by cough, dyspnea, myalgia, headache, and diarrhea. According to Lai et al., most patients had a normal white cell count, but about 56.8% of patients had leukopenia on smear.[9] Huang et al. studied the patients over hospital stay and found that the median interval between the onset of illness and hospital admission was 7 days, dyspnea was 8 days, acute respiratory distress syndrome was 9 days, mechanical ventilation was 10.5 days, and intensive care unit (ICU) admission was 10.5 days. Most patients had leukopenia and lymphopenia, and elevations in prothrombin time and d-dimer were more common among ICU admissions. About 37% of patients had an elevation in the aspartate aminotransferase levels; however, most patients had a normal procalcitonin level in the absence of a secondary superinfection.[12] Almost all patients at presentation had bilobar consolidation on chest computed tomography imaging, which on resolution showed ground-glass opacities.[12] A retrospective cohort study conducted by Chen et al. in Jinyintan Hospital and Wuhan Pulmonary Hospital, Wuhan, China, showed that the early predictors of poor prognosis include older age, higher qSOFA, and d-dimer value >1 μg/L.[6]
| Diagnosis | | |
Case definitions have been issued by different centers such as the United States Centers for Disease Control and Prevention, the WHO, and the European Centre for Disease Prevention and Control, to determine who should have diagnostic testing performed. The WHO defines a suspected case as “a patient with acute respiratory illness (i.e., fever and at least one sign or symptom of respiratory disease, e.g., cough or shortness of breath) AND with no other etiology that fully explains the clinical presentation AND a history of travel to or residence in a country, area, or territory that has reported local transmission of COVID-19 disease during the 14 days prior to symptom onset.”
The WHO recommends “collecting specimens from both the upper respiratory tract (naso-and oropharyngeal samples) and lower respiratory tract such as expectorated sputum, endotracheal aspirate, or bronchoalveolar lavage.” In the laboratory, amplification of the genetic material extracted from the saliva or mucus sample is through a reverse transcriptase-polymerase chain reaction (RT-PCR), which is searched for those portions of the genetic code of the CoV that are conserved. The WHO also designates definition for a “probable case” who is a suspected case with inconclusive laboratory testing for the infection. With respect to recommendations for follow-up of contacts, the WHO defines contacts as a “person providing direct care to a patient without using proper personal protective equipment, staying in the same close environment as a COVID-19 patient and travelling in close proximity (<1 m separation) with a COVID-19 patient.”[13]
| Potential Treatment Options | | |
There has been no definite treatment option for COVID-19 agreed upon as yet. The treatment options tried have varied from oral antiviral therapy and mechanical ventilation to extracorporeal membrane oxygenation in certain centers. In a study done by Wang et al., from the Zhongnan Hospital of the Wuhan University, all the patients were treated with antibacterial agents, 90% with antiviral agents, and 45% with methylprednisolone, however, with no “effective outcome.”[14] Potential treatment options discussed in the pharmacologic management of COVID-19 is lopinavir/ritonavir. Lopinavir/ritonavir was found to have in vitro activity against the SARS-CoV[15] and was used as a therapeutic option along with a short course of corticosteroid against the SARS-CoV in 2003. According to Chu et al., patients treated with lopinavir/ritonavir and corticosteroids ran a milder course of illness with respect to diarrhea, recurrence of fever, and worsening of chest radiographs.[16] Remdesivir, a novel nucleotide analog prodrug in development, is being touted as a prospective drug in the treatment of SARS-CoV-2. The first case report of SARS-CoV-2 in the United States, published by Holshue et al., reports improvement in the clinical condition of the patient after being started on intravenous infusion of remdesivir for compassionate usage following a week of vancomycin infusion.[17] Two clinical trials are already underway in China to further explore the therapeutic effects of remdesivir. Another drug which was found to be effective against the SARS-CoV was the widely prevalent chloroquine. A 2005 study by Vincent et al. showed that chloroquine had antiviral activity against SARS-CoV before the initiation of infection as well as after the establishment of infection, thereby suggesting both prophylactic and therapeutic potential in an outbreak.[15] China has also recently approved the disease-modifying, antirheumatic, interleukin-6 receptor antagonist tocilizumab for use in severe infections even though trials are only underway as of now.[18]
In spite of the myriad of options being explored, the treatment for COVID-19 largely remains to be meticulous supportive care. For patients with suspected COVID-19, with mild symptoms, the WHO has issued recommendations for supportive management at home, including management of the contacts.[19] Patients who have severe disease and thereby require in-hospital management, often need high-flow oxygen and noninvasive positive pressure ventilation. However, the safety of such means of supportive care in the absence of adequate isolation facilities needs to be reassessed considering the aerosol generation associated with such treatment modalities.[20]
| The Road Ahead | | |
The striking difference between SARS-CoV, MERS-CoV, and SARS-CoV-2 and other seasonal influenza, of the kind of the 2009 H1N1 influenza A pandemic, is the lack of a definitive therapeutic agent like oseltamivir at the onset of the outbreak. This explains the high mortality associated with the coronavirus infections – 11% case fatality rate in SARS-CoV (8422 cases with 916 deaths at the end of the epidemic)[21] and 35% case fatality rate in MERS-CoV (2298 cases with 811 deaths as of January 2019),[22] which are markedly low when compared to the case fatality rate range of 0.0003%–1.446% in the 2009 H1N1 influenza A.[23]
COVID-19 could combine both worlds, which means that it could be a pandemic close to the proportion of the 2009 H1N1 pandemic with a case fatality rate closer to the SARS-CoV and MERS-CoV. This could also mean that we are looking at one of the greatest public health challenges of our times. But for the first time, we may be looking at a pandemic which could be controlled on a short-term basis and prevented on a long term with adequate research and clinical trials for newer therapeutic agents.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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