Current Status
Total cases of COVID-19 in Nepal are 16945 as of 13th July 2020 with total cured and deaths are 10294 and 38, respectively. The district wise confirmed cases with cured and death due to COVID-19 in Nepal is presented in Table 1. The first COVID-19 index case was reported in Nepal on 23rd January 2020 when a 31-year-old student, who had returned to Kathmandu from Wuhan, China (epicenter of COVID-19), was also the first case reported in South Asia. The second case was confirmed on 23rd March 2020 in Kathmandu after two month later of the first case. Then the Federal Government of Nepal formally declared a nationwide lockdown from 24th March 2020. The first local transmission and first death of COVID-19 was reported on 4th April 2020 in Kailali and on 14th May 2020 in Sindhupalchwok district, respectively. Globally, as of 13th July 2020, over 11 million were confirmed in 213 countries with reported deaths and cured are 0.55 million and 4.45 million, respectively. The fatality rate and cured rate in Nepal due to COVID-19 were 0.21% and 60.75%, respectively while of the globe were 4.34% and 58.13%, respectively. As of 13th July, 2020, Nepal ranks on 61th position in global context, 23rd rank in Asia in number of infected cases. Moreover, on the South Asian Association for Regional Cooperation it ranks on 6th position on infected cases per million populations (Fig. 2).
The province wise total cases reported is highest in Province 2 (n = 4,348) followed by Province 5 (n = 4,071) and Sudurpaschim (n = 3,936) (Table 2). As depicted in Table 1, the confirmed cases of COVID-19 are distributed throughout the country with all the administrative districts. However, as of 13th July, 2020, 7 districts namely, Paachthar, Dhankutta, Bhojpur, Rasuwa, Manang, Mustang and Humla had no active cases. The total number of confirmed cases is highest in the Rautahat district (n = 1,453) followed by Kailali (n = 922) Dailekh (n = 812), and Kapilbastu (n = 765) and lowest in Manang (n = 1) and Mustang (n = 1) followed by Humla (n = 2) and Solukhumbu district (n = 2) districts (Table 1).
The detailed cumulative trend analysis of COVID-19 in Nepal is present in Fig. 3. The total number of recently confirmed cases in Nepal rapidly increased from 11th May to Ist July, 2020 then sluggish up to 13th July though ease in lockdown started from 11th June 2020. However, earlier studies showed an increasing trend with the ease in lockdown for the number of corona cases [27]. Moreover, only one hundred fifty-five new cases have been reported on 13th July 2020.
Age and gender wise distribution of confirmed COVID-19 cases are illustrated in Fig. 4 and Fig 5. The largest number of infected cases was reported in the age group 21-30 years, which accounted for 37.39% (n = 6337) followed by the age group of 31-40 years which accounted for 23.06% (n = 3909) over the study period. However, death rate was higher in age group 41-50 (n = 11), which contributed to 28.94% of total death cases. The age wise distribution of the disease, infected persons and death cases are contrasting to the many other countries around the globe, is one of the key finding of this study.
From Fig. 5, a higher proportion of male compared with females in the different age groups was infected. Among 16,945 confirmed cases, 14,588 were males and 2,357 were females, with a male-to-female sex ratio of ~6.2. Similar to our study one study by Jordan et al. (2020) concluded infection risk was higher among men than women however the ratio was comparatively lower than the present study [27]. In context to Nepal, the few reasons behind this may be a larger number of male immigrants from other countries, particularly from India due to cross country open borders. Further steroids, especially low levels of estrogen and X-linked gene activity are also attributed for high risk of COVID-19 in Male [28]. Importantly 97% of COVID-19 cases were immigrants from India [29], is one of the serious matters of concern for all levels of governing bodies in Nepal. In contrast to our study, the gender wise distribution pattern of COVID-19 cases in Italy stated the number of female cases to be slightly more than males [30], concluding heterogeneity in infection rates among gender in different countries. Higher numbers of infected cases were males of age group 21-30 years followed by age group 10-20 years. Likewise, females of age group 21-30 years followed by age group 31-40 years were infected. In context to the death cases male of age group 41-50 years (n = 9) and female of age group 21-30 years (n = 5) have major contributions. Overall, men's death was 3.75 times the death rate of women. The study by Jin et al. [31] and Shim et al. [32] also stated males are more at risk of mortality; however the death ratio was observed 2.4 and 2.75, respectively.
Spatial distribution of COVID-19
Geographically, Nepal is divided into three distinct ecological regions, Mountain in north, Hilly in middle and lowland plain in South. The spatial distribution of COVID-19 confirmed cases is presented in Fig.6. The reported cases in the plain region are relatively higher than the Hilly and Mountain regions. More than 70% of total confirmed cases are reported from the lowland -plain areas. The main reason for the high number of confirmed cases in the lowland plain region is most probably due to the open boundary with India [29] and major cities with high population density in the plain region [33, 34]. However, the numbers of death cases are higher in hilly regions compared to plain regions (Table 2; Fig. 6). One of the reasons behind the higher death cases in hilly regions may be due to lack of rapid access to health facilities [35]. While comparing the cases with India as of 13th July of 2020 was 0.9 million and ranked in the top three in the world. Huge numbers of Nepalese are in India for different purposes such as working, studying and other different business purposes. Large number of people entered Nepal without maintaining proper physical distance after declaring the lockdown in India which causes the outbreak of COVID-19 in Nepal.
Prospects for controlling future pandemics of SARS-CoV
With the global scenario of SARS-CoV in 2003 (SARS-CoV), 2012 (MERS-CoV) and 2019 (SARS-CoV-2), alarm world for the next outbreak sooner or later. Based on the progress made in medical sector, as well as science and technology to date, the experiences gained from numerous outbreaks of infectious diseases in the past few centuries and decades, we suggest the necessity of some future preventive perspectives to be initiated to stop or lessen the impact of upcoming pandemics. So, for the foreseeable future we must first deal with the ongoing pandemic and future threat by anticipating as far as possible catastrophic.
Identification of the key medical and social elements
One of the key determinants that profound the mortality and morbidity of people due to infection by SARS-CoV-2 is social and economic status [36, 37]. Some of the common sources could be the animal trafficking [38, 39], poor sanitation and hygiene of livestock workers [40, 41], reservoir intermediate animal sources [42] increase the risk of emergence of zoonotic disease. Anti-smuggling operations and close monitoring of rearing of wild and domestic animals and associated workers hygienic status is important to break transmission link of infectious agents. Cross country open borders have brought challenges of viral spread via immigrants in many countries around the world, and Nepal is one of the examples. The connection between socio-cultures, climate change, humidity and seasonal variability assume that the risk of transmission of SARS-CoV-2 does appear to be the greatest [43, 44]. Additionally, variation in food availability and food intake, age, and sex are important factors which could also play a role in the SARS-CoV-2 notification variability [45]. Ethnicity is another key player for increased risk of acquiring SARS-CoV-2 infection, for instance, studies have revealed that the Black, Asian and Minority Ethnic individuals are more prone and worsen clinical complications from COVID-19 compared to White individuals [46-48]. Further, good food practice strategies to boost immune responses with immunity eliciting (boosting) agents have positive impact in nullifying the severity of SARS-CoV-2 [49]. Assessments of global changes in present endemic/pandemic [50, 51] are crucial to identify impacts for future endemic/pandemic and their mitigation and management. Likewise, technologies and devices for effective tracking and tracing, rapid screening of infections [52-54] are important to identify the current epidemic, and eliminate the future outbreaks. Increasing prevalence of SARS-CoV-2 in non-communicable diseases conditions such as obesity, high blood pressure, chronic obstructive pulmonary disease, diabetes mellitus, cardiovascular diseases, and cancer can be a clue for safety of these vulnerable groups [55]. Intermittent trends and variation in genomic changes in corona strains of animals’ analysis may have ideas for future. Pre collaboration, actions and awareness on the abovementioned social and medical determinants by government sectors, the private sector, civil society organizations non-governmental organizations, international organizations could have a positive effect on future prevention, spread and lessen the calamitous impacts of pandemic.
Treatment options for a future pandemic
SARS-CoV-2 is an enveloped positive sense, single-stranded RNA virus with 50–200 nanometers in diameter with four major structural proteins, spike protein, membrane protein, envelope protein and nucleocapsid protein together with several accessory proteins [56]. In addition, the close genomic relationship (>75% nucleotide identity) of SARS-CoV-2 with SARS-CoV and MERS-CoV has been a good playground for similar therapeutic insights [57]. In the current face of tragic of unavailable clinically approved vaccines or drugs for SARS-CoV-2 treatment except few antiviral agents and others (remdesivir, favipiravir, hydroquinone, azithromycin, dexamethasone) to lessen the severity of complications of COVID-19 [10] paving a way to drugs/vaccine discovery is utmost. Antiviral agents could be discovered and developed by targeting, broadly various stages of the life cycle of virus (entry, attachment, replication, transcription, translation, maturation, release) [58, 59] by currently available methods, either computational or/and traditional. And/or, targeting molecular targets such as ACE2 of human, 3CLpro protease, Nsp13 helicase of SARS-CoV-2, for instance [61, 62]. Basically, discover and/or test existing broad-spectrum antiviral drugs, screening of the all available molecular databases, based on the genomic, signaling and pathological information could lead to characterization of more effective therapeutics from present to future. Thus identifying, discovery, development of stockpile of antiviral and developing standard operating procedures for rapid deployment would be effective treatment options to cope with the disastrous impact of the future outbreak.
Next powerful weapon to combat SARS-CoV-2 at present and for future outbreak is vaccination, which has worked spectacularly well in many cases. As the structural and genomic information have been available characterization and development and distribution of vaccine for possible vaccine production strategy that undermined the ability to treat severe cases effectively could be highly counterproductive [62]. In addition, technical support, capacity building and technology transfer for SARS-CoV-2 vaccines and diagnostics to developing countries to prepare stockpiles of vaccines. Moreover, genome sequence SARS-CoV-2 displayed nucleotide identity (>75%) to the previously identified coronavirus SARS-CoV, MERS-CoV, for instance, could be very helpful in developing broad-spectrum monoclonal antibodies against the plethora of coronavirus strains [63] despite of several hurdles on the counter parts. So, for the current and foreseeable future we must deal with the ongoing antiviral agent and vaccine development side by side to counter the sudden abrupt outbreak.
Epidemic preparedness of health care system
Besides non-pharmaceutical interventions, healthcare facilities and their staffs are key players in epidemic preparedness for outbreak response. The lack of progress in controlling the current pandemic of SARS-CoV-2 revealed poor settings of public health systems and services together with limited contact tracing, poor setting of quarantine, disobeying physical distancing rule and so on. Inspiring statements about bold policy changes for health system strengthening must be urgently translated into action with efficient collaboration and coordination among state, local, and territorial national and international public health agencies for full protection against the evolving catastrophic direct and indirect cost of illness [64-68]. Addressing all barriers (Fig.7) is a tall order and will require political will on the highest level, stimulated by forceful grassroots demands [69].
Investing in ethno-medicine research
Calamitous outbreaks have been recorded from ancient periods in the history of human civilization, including Spanish Flu, Hong Kong Flu, SARS, H7N9, Ebola, Zika, to name a few. These viruses explode informally as endemic, epidemic and pandemic, in some cases remaining as a seasonal flu and infecting millions of people and thousands of deaths each year [3, 70, 71]. Based on the historical records, despite of some drawbacks, herbal drugs has been used in the traditional medicine for treatment of different disease including COVD-19, Astragali Radix , Glycyrrhizae Radix Et Rhizoma , Lonicerae Japonicae Flos and Fructus forsythia, to name few [72-73]. The era of antiviral therapy can be traced back to the 1960s, since then over 60 clinically efficacious antiviral compounds have been discovered till date. However, mostly, if not all have some limitations, ranging from poor bioavailability to toxic side effects and drug resistance with some virus where no effective drugs or vaccines exist [74]. After some period (1990-2010s AD) of pace dawn of discovery of drugs from plants origin there is again resurgence of research in ethno-medicine-based drug discovery. In the current era, in many developed countries research institutes, universities and pharmaceutical laboratories as well as in the clinics thereof priorities have been given to scientific research on medicinal plants. In present scenario about 35 percent of western medicines originated directly from natural products or their derivatives {plants (approx. 25%), microorganisms (approx. 13%), animals (approx. 3%) and derive from natural products (approx. 14%)} [75-77]. Therefore, medicinal plants and their bioactive metabolites are the main focus of interest and have several advantages over the synthetic drugs due to their broad therapeutic potency, limited side effects and their ongoing human trial for a long time. Thus, the research on ethno-medicine is a key step for transferring antiviral agents from the impatient to the patient. To catalyze this transformation and pave the way for future research crucial priority for scientific investment is unavoidable. Ensuring full and continued funding and implementation of all components of the SARS-CoV-2 is the highest priority for all countries for better, wise and wider use of existing technologies to dissect the antiviral drugs from natural products.