BACKGROUND: The pandemic of Coronavirus Disease 2019 (COVID-19), one of the most infectious diseases in the modern history, is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and has had a profound health and economic toll, globally. This paper identifies the overall health status associated with COVID-19 pandemic in all 7 provinces of Nepal, a developing country in South Asia, analyzing data from January 2020 to February 2022. It focuses on the SARS-CoV-2 prevalence, transmission through wastewater and other routes, diagnostics, treatment options, and alternative medicines, thereby offering key perspectives for its management.
MATERIALS AND METHODS: Studies regarding coronavirus spanning the 2017 to 2022 period were searched on the web, Nepalese database, and Web of Science. Refined criteria included SARS-CoV-2 in wastewater of Nepal or worldwide. Demographic data (sex, age-group, and geographic location) were also obtained from websites and relevant reports of the Ministry of Health and Population (MOHP) of Nepal, ranging from January 2020 to February 2022. Moreover, trends concerning lockdown, business, and border activities in Nepal between February 2020 and October 2020 were evaluated. The viral dissemination pathways, diagnosis, and available treatment options, including the Ayurvedic medicine, were also examined.
RESULTS: Aerosols generated during the hospital, industrial, recreational, and household activities were found to contribute to the propagation of SARS-CoV-2 into environmental wastewater, thereby putting the surrounding communities at risk of infection. When lockdown ended and businesses opened in October 2020, the number of active cases of COVID-19 increased exponentially. Bagmati Province had the highest number of cases (53.84%), while the remaining 6 provinces tallied 46.16%. Kathmandu district had the highest number of COVID-19 cases (138, 319 cases), while Manang district had the smallest number of infections (81 cases). The male population was found to be predominantly infected (58.7%). The most affected age groups were the 31 to 40 years old males (25.92%) and the 21 to 30 years old females (26.85%).
CONCLUSION: The pandemic impacted the public health and economic growth in our study duration. SARS-CoV-2 was prevalent in the wastewater of Nepal. The Terai districts and the megacities were mostly affected by SARS-CoV-2 infections. Working-age groups and males were identified as the highest risk groups. More investigations on the therapeutic and alternative cures are recommended. These findings may guide the researchers and professionals with handling the COVID-19 challenges in developing countries such as Nepal and better prepare for future pandemics.
Background
Emerging infectious diseases (EIDs) present one of the greatest challenges to public health in the 21st century. An emerging virus, depending on its potential to spread among humans, may cause individual or sporadic cases, culminating in a localized outbreak requiring public health intervention, or, in the worst-case scenario, a widespread epidemic, or worldwide pandemic.1 The novel Coronavirus Disease 2019 (COVID-19) is a new respiratory disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) that is causing worldwide public health and economic challenges and has been recognized as a pandemic by the World Health Organization.2 The virus was first reported in Wuhan, Hubei Province, China, in December 2019.2,3 SARS-CoV-2 is an enveloped and positive single-stranded RNA virus belonging to the ß-coronavirus genus.2–4 SARS-CoV-2 holds high homology with SARS-CoV and targets angiotensin-converting enzyme receptor-2 (ACE2) for the viral attachment.4 A schematic depicting SARS-CoV-2 structure and pathogenesis is presented in Figure 1.5 There are very few studies on the transmission of SARS-CoV-2 through treated or untreated wastewater from advanced countries; however, COVID-19 surveillance of wastewater in developing countries has not been reported adequately.6 There is thus a need to study the presence of SARS-CoV-2 in wastewater in the developing countries like Nepal.
On 24th January 2020, the first case of COVID-19 was reported in a Nepalese student, who had recently returned from China to Nepal, and the second case was identified about 2 months later in a person returning from France.7 A complete genome sequence of SARS-CoV-2 strain from a Nepalese patient with COVID-19 showed 99.6% identity with SARS-CoV-2 reference genome and the full-genome comparison of the isolate revealed >99.99% identity with 2 previously sequenced genomes available at GenBank (MN988668 and NC045512) for SARS-CoV-2 from Wuhan, China, and >99.9% with 7 additional sequences: MN938384.1, MN975262.1, MN985325.1, MN988713.1, MN994467.1, MN994468.1, and MN997409.8,9 The majority of COVID-19 cases were reported to be asymptomatic. The likelihood of COVID-19 outbreak was noticeably underestimated in Nepal during the early phase of the pandemic and there was a subsequent rise in cases over time.10
Notably, the healthcare system in Nepal was not prepared to manage such an outbreak in terms of physical facilities in the hospitals, availability of health care professionals, and arrangement of diagnostic as well as safety materials for the frontline healthcare professionals. There were misconceptions spread in the society that the Nepalese people are resistant against the COVID-19 for some unknown reasons. They also believed that their culinary practice and traditional medicine were effective against the disease, albeit with no scientific evidence. On one hand, there has been a challenge, particularly, for healthcare professionals in tackling COVID-19 with utmost precautions and with limited resources. On the other hand, there was a challenge for the scientific community to carry out a comprehensive analysis of the trend of the disease outbreak and recommend the government for efficient strategy formulation.
The population living under the absolute poverty line is 18.7% of the total population according to the Department of Information, Nepal. The population covered by health insurance in the base year 2018/19 was reported to be 7%.11 The present health system’s capacity to respond to COVID-19 is inadequate. According to the Ministry of Health and Population Nepal in 2020, there were 26 930 hospital beds, 1595 ICU beds, 840 ventilators, 194 hospitals with ICU facilities, 111 hospitals with COVID clinics, 13 Level-1 COVID hospitals, 12 Level II COVID hospitals, 3 Level III COVID hospitals, and 3076 isolation beds.12 Some hospitals were designated to treat COVID-19 cases in all 7 provinces of Nepal. But there was negligence to extend strategies to trace, isolate, test, and treat since efforts were deficient to standardize testing facilities and manage isolation centers for COVID-19 patients. The panic and psychological impact regarding COVID-19 led to losses of lives by non-COVID-related diseases in the early period of the pandemic13 as well as an increase in suicide rates.14 Later, the deaths continued since the strategies were inadequate to manage COVID-19 and non-COVID-related diseases in those hospitalized. People feared visiting the hospital to treat minor illnesses, which might be attributed to the increased severity of COVID-19 patients with comorbidities.
Herein, this study summarizes the overall status of COVID-19 in a developing country, Nepal, with SARS-CoV-2 transmission through wastewater and other routes; disease cases in all 7 provinces; diagnostics, treatment options, and alternative medicines; and offers perspectives in managing the disease and any future pandemics. The systematic literature review was based on the search criteria consisting of keywords: “coronavirus,” “coronavirus in Nepal,” and “coronavirus in wastewater,” and the publications from 2017 to 2022 were included (Figure 2), which was further refined to “coronavirus in wastewater” and “coronavirus in wastewater of Nepal”: the 2 broader categories in the Web of Science. Also, data reported from January 2020 to February 2022 from the Ministry of Health and Population, Nepal, were included to determine the impact of pandemic on different age-groups, sexes, and by geography. Moreover, data ranging from February 2020 to October 2020 were used to evaluate trends related with lockdown, business, and border activity. The data were visualized in the form of graphs (GraphPad prism 8.4.3) and tables, the conceptual figures were created in Adobe Illustrator 2020, the geographic maps were created using AcrGIS, and the statistical calculations were performed in MS-Excel 2007. The findings are novel and may guide researchers and professionals working on managing COVID-19 in a developing country Nepal for better risk assessment and management.
SARS-CoV-2 in Wastewater
Wastewater surveillance is an approach to monitoring diseases via wastewater effluent.15 SARS-CoV-2 can disseminate through water and wastewater, leading to potential environmental transmission as shown in Figure 3.16 The potential harbored by SARS-CoV-2 for transmission via fecal-oral and aerosol routes poses an imminent challenge to comprehend the survival of the virus circulating in the environment.17 The presence and evolution of SARS-CoV-2 in waters, soils, and other environmental compartments may pose a public health risk.18 SARS-CoV-2 enters wastewater through the residential, industrial, and quarantine (isolation) facilities with COVID-19 patients.19
In Nepal, SARS-CoV-2 ribonucleic acid (RNA) was found in 60% (50/84 samples) of wastewater and river water samples analyzed.20 Different studies have documented the presence of SARS-CoV-2 RNA in wastewater from different countries.21–37 In the neighboring country, India, the viral genome was detected in the wastewater system.38 Viral shedding through the digestive route seems to last longer than the shedding through the respiratory tract.39 The impact of lockdown on SARS-CoV-2 dynamics was assessed using viral genome quantification in Paris wastewater and a significant decrease in the number of genome units was recorded, which coincided with the expected decline in the number of new COVID-19 cases with the length of lockdown.40 The possibility of secondary transmission via wastewater should not be overlooked, as the virus has been found in human feces and wastewater samples from many countries, with possible cases of transmission still being debated.41 Some coronaviruses can potentially survive in the gastrointestinal tract and spread via fecal-oral route or via inhalation of contaminated wastewater droplets.42
The design encompassing wastewater plumbing system could allow harboring pathogenic microorganisms and has been suggested to hold the potential for enabling airborne transmission of the viruses, such as SARS-CoV-2, upon aerosol generation. Further, self-isolation and official quarantine centers for infected people could serve as a hotspot for virus shedding into the system.43,44 The possibility of extended duration of viral shedding in feces, for nearly 5 weeks after the patients’ respiratory samples tested negative for SARS-CoV-2 RNA and the virus remaining viable for days in feces, may contribute to fecal-oral transmission.45,46 The presence of SARS-CoV-2 in the infected person’s feces and urine, even after viral clearance in the respiratory tract, as well as its presence in untreated wastewater, may elevate the likelihood of future fecal-oral transmission to potential intestinal infection.6,47 However, the presence of viral genetic materials in stool does not always mean that viable infectious virions are present in feces or that the virus can or has spread by fecal-fomite, fecal-oral, or fecal-aerosol/droplet transmission.48,49
Wastewater surveillance includes the concentration of SARS-CoV-2 RNA from wastewater in a catchment or sampling point and enumeration of viral RNA copies using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR).36 However, the problems associated with biomedical wastewater treatment and disposals are of public health concern, particularly in developing countries like Nepal where hazardous waste landfills are absent.50 Longitudinal analysis of wastewater can provide population-level estimates of the burden of SARS-CoV-2 where in-person or at-home testing may not be available.51 SARS-CoV-2 in wastewater may reflect a potential health threat to individuals and has the potential to spread through aerosol inhalation or ingestion when the virus remains infectious in wastewater. Various coronaviruses could be cultured for a few days from wastewater.52,53 Also, the enteric transmission of SARS-CoV-2 may be possible. Environmental surveillance of SARS-CoV-2 could serve as a data source and indicate whether the virus is circulating in the community or not.33,54
SARS-CoV-2 Transmission and Cases in Nepal
While the source of SARS-CoV-2 is still unknown, bats and pangolins have been suspected, crossing the species barrier, and rapid human-to-human airborne transmission has been established.55–57 Viral transmission could also occur through other routes including fomite, fecal-oral, blood-borne, mother-to-child, and animal-to-human routes.58–60
Nepal is not an exception to COVID-19 and encountered challenges to prevent the spread of infection. Nepal was under complete lockdown from March 24, 2020, for several months in an attempt to control COVID-19 and prevent its spread into the community.61 At the same time, a large number of Nepalese citizens returned from highly infected areas like India and China through open borders and entered different parts of the country without quarantining. When the lockdown ended and people returned to their normal schedule in October 2020, the cases increased exponentially (Figure 4). Gradually, COVID-19 spread all over Nepal, with an increase in the number of new cases and deaths. Among them, most of the infected patients were reported from Bagmati Province. In Nepal, research documented a possible link between COVID-19 and temperature indicators, showing increased transmission of the disease in winter.62 This created an alarming scenario in a low-income country Nepal with an inadequate healthcare system. The data from January 2020 to February 2022 demonstrated the highest numbers of cases for Kathmandu district, while the lowest occurred in Manang district (Table 1). In Nepal, the total number of cases until February 17, 2021, was 974 493. The highest total cases were found in Bagmati Province (53.84%) followed by Province 1 (13.07%), Lumbini province (11.18%), and Gandaki province (9.55%), respectively. The cases were low in Karnali Province (2.44%), Sudurpashchim Province (4.5%), and Madhesh Province (5.42%). Figure 5 shows the COVID-19 cases trend district-wise and province-wise for Nepal for the period January 24, 2020 through February 17, 2021. The Terai region, including the Kathmandu valley, had a significant number of cases. This could be linked to Nepal’s open border with India on 3 sides: east, south, and west, as well as influx from COVID-19 affected areas nearby.61 Also, megacities may have a greater number of cases because of dense populations.63 The gender-wise distribution of COVID-19 cases is presented in Figure 6. Data showed that males were predominantly infected (58.7%) compared to females (41.23%) (Figure 6). The age group between 31 and 40 years old males were infected the most (25.92%), while the females aged 21 to 30 years old were infected the most (26.85%) (Figure 7). The reason may be these age groups belong to the active working population in Nepal. The age group 80+ were the least infected, likely due to the low number of elderly population above 80 tested. Males were more symptomatic than females. A meta-analysis further corroborated that females could present COVID-19 cases in asymptomatic form compared to males.64
Table 1.
District-wise highest and lowest cases of COVID-19 in 7 provinces of Nepal (January 24, 2020 through February 17, 2022).
The first death in Nepal was a 29-year-old new mother with an unknown mode of transmission on May 16, 2020, and by June 21, there were 23 deaths reported. Surprisingly, most of the deaths happened outside of hospitals, and COVID-19 was confirmed postmortem.65
Laboratory Diagnosis to Detect SARS-CoV-2 in Nepal
As a low-resource country, Nepal has had suffered a profound impact on the clinical microbiology laboratories over the course of this pandemic.66 Not only clinically, but also technologically and logistically, rapid and accurate detection of this novel virus offers considerable challenges. Before laboratory diagnosis, to categorize the suspected patients of COVID-19, the clinicians should observe the following symptoms: fever or symptoms of lower respiratory infection, such as cough or shortness of breath, fatigue, dyspnea, sore throat, headache, conjunctivitis, and/or gastrointestinal issues.67–69
The gold standard for the detection of SARS-CoV-2 is the identification of the viral genome targets by nucleic acid amplification test (NAAT), such as real-time reverse transcription-polymerase chain reaction (rRT-PCR), used globally for the diagnosis of COVID-19 in the upper respiratory samples during the first week of infections. It uses the TaqMan fluorogenic probe-based chemistry and 5′-nuclease activity of Taq DNA polymerase.70
Nonetheless, rapid diagnostic tests (RDTs), such as antigen-detecting RDTs (Ag-RDT) and antibody-detecting RDTs, virus isolation (culture method), electron microscopic examination, complete genomic sequencing technique (Meta-genomics, next-generation sequencing), and isothermal-CRISPR-based diagnostics have been used for the detection of SARS-CoV-2.71–73 However, each method presents its limitations. Comparative study of different diagnostics molecular technologies has revealed that CRISPR-COVID had a 100% specificity and 40 minutes as the reaction turn-around time (TAT); RT-PCR-COVID with 90.4% specificity and 1.5 hours TAT; and NGS with 100% specificity and approximately 20 hours TAT.71 Whereas antigen and antibody-based rapid immunoassays with a wide range of sensitivity and specificity are also available in the market.72
In Nepal, confirmatory test for COVID-19 and/or detection of genomic material (i.e., RNA) of SARS-CoV-2 involves the rRT-PCR method. However, serology-based immunoglobulin (IgM and IgG) antibody tests and antigen tests are also being introduced as supplementary and seroprevalence tools for community surveillance.74 PCR assays were rapidly deployed in the country during the early stages of the pandemic and have formed the cornerstone of detection. The central government agencies also rapidly deployed funding mechanisms for developing novel testing strategies. The RDTs didn’t exhibit enough reliable performance (sensitivity and specificity) and were not recommended for stand-alone use to guide decision-making in any setting. A similar response was found in her southern neighbor, India.75
Upon meeting the national testing guidelines, specimens collected from the upper respiratory tract include nasopharyngeal (NP) swab and oropharyngeal swab: synthetic fiber swabs with plastic shafts are preferred over calcium alginate swabs or cotton-tipped swabs with wooden shafts, for molecular diagnosis. The swabs are immediately placed in sterile tubes containing 2 to 3 mL of viral transport media (VTM). However, other possible samples include bronchoalveolar lavage, tracheal aspirate, NP aspirate, nasal wash, saliva, sputum, blood/paired serum, urine, and stool for detection of the viral RNA.76–79 Clinicians are advised to wear proper personal protective equipment (PPE) during specimen collection, pack the specimens in a triple packaging system, and maintain the cold chain for the transport of specimens in VTM before processing.80,81 However, many affluent countries have also encountered challenges in the test delivery, specimen collection and transport, and limited testing. These challenges persisted greater in low-resource settings as in Nepal.81,82
Tests are performed in designated laboratories for patients meeting the case definition of COVID-19 following clinical observations and national guidelines. Diagnosis of COVID-19 is ultimately confirmed by rRT-PCR.83,84 Although RT-PCR is considered the standard laboratory test for the diagnosis of COVID-19, it may also yield a false negative/positive result in some cases.85 In the early stage of the disease, several cases with false-negative/positive RT-PCR results were reported probably because of inadequate viral loads in the sample and/or technical issues during nucleic acid extraction.86
Molecular tests form the basis for confirming COVID-19, whereas computed tomography (CT) scan may support the diagnosis87 but serological tests for SARS-CoV-2 that are also widely available play an increasingly important role in understanding the epidemiology of the virus and in identifying populations at higher risk for infection.66,74,88,89 In cases with typical clinical manifestations, chest CT may prove to be an invaluable asset because it may show characteristic features of the disease even when the RT-PCR screening test is negative.90,91
Treatment of COVID-19 in Nepal
The antiviral therapeutics used globally against SARS-CoV-2 infection were not particularly designed to act against SARS-CoV-2. Camostatmesilate (Foipan™) and Nafamostatmesilate (Buipel™) are serine protease inhibitors, which target TMPRSS2.92,93 An antimalarial drug Chloroquine phosphate (Resochin™) targets ACE2,94,95 and hydroxychloroquine (Quensyl™, Plaquenil™, Hydroquin™, Dolquine™, Quinoric™) acts against endosome and pH.95–97 Remdesivir is an adenine nucleotide analog targeting viral RdRp.98–100 Favipiravir (Avigan™) also targets RdRp.101 Lopinavir/Ritonavir (Kaletra™) targets viral proteases.102,103 Umifenovir (Arbidol™) targets membrane fusion and clathrin-mediated endocytosis.104 These drugs are under various phases of clinical trials against SARS-CoV-2 infection.
In Nepal, Remdesivir is the major potential drug under evaluation. Further, plasma therapy is also under trial. On 9th August 2020, the Government of Nepal granted permission to use Remdesivir in COVID-19 patients as an experimental drug. The Ministry of Health and Population (MoHP) and the Department of Drug Administration (DDA) of Nepal authorized the import and usage of Remdesivir for treating COVID-19 and delegated authority to Nepal Health Research Council (NHRC) to oversee its administration as an experimental use drug (Nepal Health Research Council).105
However, it was found that Remdesivir use was not statistically associated with a difference in time to clinical improvement in SARS-CoV-2 infected patients but was found effective based on individuality.106 Patients receiving Remdesivir presented complications, including hypersensitivity reactions such as anaphylactic and infusion-related reactions.74 The drug has displayed a mixed result in COVID-19 patients and has side effects to the level of acceptance.107
Treatment Options Against SARS-CoV-2 Infection in Nepal
Remdesivir
Remdesivir (Veklury) was approved by the US Food and Drug Administration (FDA) for use against mild-to-severe COVID-19.108 The median time to recovery was significantly reduced by 5 days in patients that received Veklury (10 days for the recovery for Veklury group compared to 15 days for the placebo group). The odds of clinical improvement at day-15 were also statistically significantly higher in the Veklury group compared to the placebo group. The overall 29-day mortality was 15% for the placebo group and 11% for the Veklury group; this difference was not statistically significant.104 In a large study conducted under the SOLIDARITY trial (a World Health Organization-sponsored, open-label, randomized trial), that included 12 000 patients in 500 hospital sites in over 30 countries, the study did not find a statistically significant difference in mortality between the Veklury group and the standard-of-care group.106 Remdesivir has been shown to speed up the recovery rate in hospitalized patients requiring supplemental oxygen but the drug alone is not adequate to solve the issues arising from the pandemic.109
Convalescent plasma therapy
Clinical trials on the use of convalescent plasma therapy against SARS-CoV-2 infection have been conducted in Nepal.110 Immune-based therapy consists of convalescent plasma and immunoglobulins, interleukin-1 (IL-1) inhibitors, interleukin-6 (IL-6) inhibitors, and other immuno-modulators. Blockage of IL-6 and IL-1 and inhibition of Janus Kinase (JAK) may lead to treating systemic inflammation associated with severe COVID-19.111 Convalescent blood products consist of convalescent whole blood or convalescent plasma or convalescent serum, pooled human immunoglobulin for intravenous or intramuscular administration, high-titer human immunoglobulin, and polyclonal or monoclonal antibodies.112 Previous studies in the United States113 and China114–117 reported plasma therapy as an option for treatment against severe COVID-19 but more clinical trials are needed to confirm its proposed efficacy. In Nepal, convalescent plasma showed beneficial effects against COVID-19, but larger, randomized controlled trials are required to confirm its efficacy.118
Ayurveda and alternative treatments in Nepal
The Ayurvedic medical system has its origin in the Indian subcontinent.119 Research published over the years in Ayurvedic and traditional Chinese medicine (TCM) have demonstrated that herbs and/or TCM can limit viral replication, limit virus entry and attachment to the host cell, and promote the patient immune system. For example, medicinal herbs with immuno-modulatory and antioxidant characteristics, such as ashwagandha (Withania somnifera), have been documented to enhance immune response and reduce viral replication.120 Tulsi, haldi (turmeric), giloy, black pepper, ginger roots, cloves, cardamom, lemon, and ashwagandha were among the phytochemical and antiviral compounds evaluated in a recent study in the hopes of finding a cure for COVID-19.121 To investigate the antiviral effect of phytochemical components and bioactive compounds found in herbs, researchers docked them with distinct coronavirus target proteins such as viral capsid spike and protease. The study indicated that certain phytochemicals used in traditional medicine had a high affinity for viral proteins, making them potential candidates for target drug design.122
A research compared the Ayurvedic protocols suggested by the governments of Nepal and India.123 There is a lot of evidence that the Ayurvedic and traditional systems of medicines offer excellent potential in dealing with COVID-19 pandemic and other epidemics that the society may encounter in the future. Altogether, during this pandemic about 60 medicinal plants belonging to 36 families were utilized in Nepal.124 There is, thus, a need to explore and utilize the traditional Ayurvedic knowledge vis-à-vis the state-of-the-art technologies to address the ongoing pandemic and prepare for any future respiratory viral disease outbreaks.
Role of Sanitation in Public Health Protection
Inadequate hygiene, sanitation, and disinfection approaches in healthcare facilities, as well as dwellings without proper wastewater disposal and management, may expose individuals to the circulating virus particles.6 Overuse of non-biodegradable plastics during the epidemic has exacerbated plastic pollution, posing a considerable health threat to land and aquatic ecosystems in Nepal.125 Access to safe water, nutritious food, and lack of sanitation and hygiene remain a challenge in most rural communities and mountain regions due to geographical challenges and lack of effective people-focused programs.126,127 Apparently healthy people were infected as a result of poorly handled quarantine and hospital waste across the country during the pandemic, as reported on national news media.128
Individuals who believe they are at risk and are aware of the seriousness of COVID-19 implications are more likely to exercise caution.129 Hand washing has been recommended as a preventative measure against the circulating and emerging SARS-CoV-2 strains.130 The survival duration of coronavirus in water environments is highly influenced by temperature, water properties, suspended solids, and organic matter concentrations, solution pH, and disinfectant dose, with the advantage that the current drinking water disinfection process effectively inactivates most bacterial and viral pathogens present in water, including SARS-CoV-2.131 The environmental discharge of inappropriately treated wastewater might expose public to coronavirus infection, underscoring the importance of proper wastewater treatment and management in the developing county Nepal.132
Conclusion and Future Perspective
The pandemic has had an impact on public health and economic growth in Nepal. SARS-CoV-2 was detected in wastewater in Nepal. SARS-CoV-2 infections were particularly common in Terai areas and megacities. Working-age groups and males were identified as the most exposed groups. With limited available healthcare resources in Nepal, it has been a significant challenge managing the growing influx of COVID-19 patients. It is, thus, critical for the hospitals and clinics in all (7) provinces to pool their resources and develop a central coordination mechanism to mobilize the available resources to effectively manage and care for COVID-19 patients. Quarantine facilities should be properly managed, staffed, and surveilled ensuring the health and safety of those that are quarantined. The coordination mechanism of the hub and satellite hospitals might be an area to work on to effectively address the issues related to limited resources and capacity building in Nepal with far limited resources to address the ongoing pandemic and prepare for any future emerging infectious diseases of epidemic and pandemic potential.
Poor sanitation and mismanagement of wastewater might serve as possible environmental factors contributing to COVID-19 transmission in Nepal; however, more focused research is needed to better understand how wastewater surveillance might help predict early transmission of SARS-CoV2 in the community and help mitigate COVID-19 spread.
Acknowledgements
We would like to acknowledge the Central Department of Microbiology, Tribhuvan University, Nepal, and the Nepal Academy of Science and Technology, Lalitpur, Nepal for their support to researchers during the COVID-19 pandemic.
Author Contributions Dev R Joshi, Sushil R. Kanel, and Lok R. Pokhrel: conceived the study design and contributed to writing and editing the manuscript. Prabin Dawadi: contributed to study design, literature search, results interpretation, data analysis, statistical output interpretations, manuscript writing. Gopiram Syangtan: literature search, results interpretation, data analysis, manuscript writing. Bhupendra Lama: data analysis, statistical output interpretations, results interpretation, manuscript writing. Rameshwar Adhikari: Commented on the manuscript. Hem R. Joshi: Statistical trend analysis. Ioana Pavel: Commented on the manuscript.
Availability of Data and Materials All data generated for this study are included in this article. The data are also available from the corresponding author upon reasonable request.