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Table 2 Research priorities based on final ranking

From: Knowledge gaps and national research priorities for COVID-19 in Iran

Domain

Title/subject

Final ranking

Epidemiology

*The comparison and evaluation of the differences in the hospitals over time in terms of symptom severity, hospitalization rate, length of intensive care unit (ICU) hospitalization, type of treatment and quality of services provided, death rate in ICU, death rate outside ICU, duration of hospitalization in ICU and comparison of mortality rates after adjusting for age, sex, comorbidity and other confounding variables

1

Epidemiology

*Calculating the economic burden of the COVID-19 disease in the country

2

Social science, public health and participation in responding to public health and clinical research

*Assessing the acceptance of interventions by people (why do people not stay at home?). Analysing people’s preferences in accepting home quarantine, especially in the final period of the outbreak where the number of new cases is low but the risk of identifying positive cases and contagion is essential for the next wave

3

Epidemiology

*Studies on prevention and studies on people's behaviour (in the workplace, shops, parks) in relation to physical distancing methods and in consideration of health recommendations

4

Social science, public health and participation in responding to public health and clinical research

*Identifying methods to reduce the psychological burden (stigma) resulting from a positive COVID test

5

Epidemiology

*Comparison of provinces, cities and even urban and rural areas in terms of preparedness, speed, social and private sector participation, hospitals’ preparedness, and disease prevention and management and its relationship with disease outbreak and mortality

6

Clinical management

*Evaluate the problems and management methods (diagnosis, treatment and follow-up) of non-COVID patients who are in critical condition

7

Epidemiology

*Analysing the factors affecting the epidemiological trend of the disease in Iran/investigating the causes of epidemic differences and clusters created at different levels, including provinces as well as cities, villages, domains and areas within different provinces and cities, nursing homes and work environments, and analysing its causes within the framework of epidemiological studies/detailed study of similarities and differences of disease clusters in specific populations such as nursing homes and work environments

8

Epidemiology

*Recording the documents and data for COVID-19 patients with the aim of evaluating diagnostic methods, disease progression, interventions and drugs used, intensive care and consequences for COVID-19 patients at the national and provincial levels

9

Epidemiology

Outbreak assessment with different methods (direct, indirect, laboratory methods and questionnaire) in different parts of the country

10

Epidemiology

*Geographical distribution of patients who attended hospitals and investigation of the problems in the management of the distribution of patients in city hospitals by university headquarters

11

Clinical management

*Evaluate and compare hospital management challenges and initiatives, including the extent of hospital preparedness, management of medical and nonmedical personnel, healthy nutrition, infection control protocol, volunteers, equipment supply, transportation of corpses, non-COVID hospitalized patients, staff stress, personnel protection, education, incentive system, etc. and their impact on hospital performance

12

Epidemiology

What social distancing interventions have been most effective in preventing or reducing the spread of COVID-19? If children are less susceptible to the disease or not transmitting the disease, should schools remain closed? *Is physical distance necessary in this group? *How much did the closure of schools reduce contacts?

13

Social science, public health and participation in responding to public health and clinical research

What are the relevant, practical and effective approaches to increasing acceptance, absorption and adherence to public health interventions for the prevention and control of COVID-19, and how can side effects be identified and mitigated rapidly?

14

Care, access and health system

*Examining the psychological condition of the families of medical staff (or other occupations that have heavy responsibilities in the current situation, such as the police)

15

Clinical management

*Assessing the extent and severity of medical errors during COVID-19 crises and emergencies

16

Epidemiology

Which restraining societal interventions can better reduce the local spread of the disease? *Should quarantine be done or not? *How contacts changed during the New Year’s holidays?

17

Clinical management

*Checking the correctness and implementation of the presented protocols/checking the clinical aspects of the disease, including guidelines for managing patients with different degrees and severity of the disease

18

Epidemiology

*The relationship between occupational factors and COVID-19 incidence, especially occupations in the health sector, personnel, contractors and volunteers working in hospitals, in clinics by type of occupation, activity and specialty considering the role of confounders (using university staff cohort, case studies, studying the details of COVID-19 patients who are working in the health sector in terms of the amount and severity of exposure, etc.)

19

Epidemiology

*What is the most accurate estimate of the basic reproduction number (R0)? Determining the contagiousness of the disease by calculating R0 and the attack rate

20

Epidemiology

*Which controlling and restraining interventions are effective in reducing the average number of cases inflicted by one individual in a mixed population (susceptible and non-susceptible) [effective reproduction number (Rt)]?

21

Clinical management

*Assessing the effective factors in the sensitivity of infection diagnosis tests with reverse transcription polymerase chain reaction (RT-PCR), including the quality of sampling from the patients, type of sample, sampling time, test site, diagnostic kit, disease severity, etc.

22

Epidemiology

*Evaluating the risk factors for COVID-19 disease infection (case–control study, use of the cohorts present in the country) and evaluation of predisposing factors (socioeconomic status, consumption of opium, different types of drugs and tobacco use including cigarettes and shisha, alcohol, obesity, nutritional status) occupational conditions, comorbidities and immune system diseases, especially HIV-positive people, travel to high-risk areas, etc.

23

Epidemiology

*Evaluation of mortality trends in non-COVID-19 patients before and after the onset of COVID-19 crisis

24

Epidemiology

Evaluation of the short-term and long-term side effects of COVID-19 disease in patients after hospital discharge, monitoring the patients who were not hospitalized

25

Clinical management

*Monitoring and evaluation of all interventions currently underway, including evaluation of the implementation of protocols for the preparation and provision of healthy nutrition for hospital staff (provision of basic materials, kitchen, distribution, quality, staff satisfaction with food, leftover food collection, etc.)

26

Clinical management

*National and provincial studies on diagnostic methods, disease progression, interventions and drugs used, intensive care, consequences of patients with COVID-19 disease to identify differences and the impact of these differences on consequences

27

Clinical management

*The performance of diagnostic and serologic, PCR, laboratory and computed tomography (CT) scan tests in diagnosing COVID-19 disease

28

Infection control

Identify the effectiveness of infection prevention and controls (IPCs) in public settings (use of masks by healthy individuals; precautions for care at home for family members and the community; education; management of corpses)

29

Social science, public health and participation in responding to public health and clinical research

*Assessing the social and psychological damage of COVID-19 at the individual level: examining the impact of lifestyle changes during quarantine and its psychological effects, people’s self-care strategies (psychologically and physically) to maintain their passion for life

30

Clinical management

*Identification and description of specific cases and syndromes of COVID-19 disease and reporting the syndromes, disease progression, performed treatments and effects of drugs and performed treatments

31

Social science, public health and participation in responding to public health and clinical research

Assess the level of anxiety and mental security in children

32

Epidemiology

*The impact of the COVID-19 epidemic on incidence, prevalence and spread of other diseases

33

Social science, public health and participation in responding to public health and clinical research

Identify the best ways to engage the community quickly and regularly and encourage them to participate in clinical trials

34

Social science, public health and participation in responding to public health and clinical research

*Reasons for the spread of alcohol poisoning and its association with the COVID-19 epidemic (are alcoholic drinks which have always been ingestible a problem, or do people mistakenly drink antiseptic alcohol?)

35

Epidemiology

Demographic data analysis of COVID-19 disease, and assessment of Lyme condition, disease severity, disease progression, differences between provinces and cities and related causes [according to demographic data (the use of hospital data can be misleading)]

36

Infectious control

Understanding IPC capacity and perceptions by using behaviour change sciences and social sciences (What are the best ways to convey IPC-related advice? The role of media coverage, home care precautions; maximum IPC decline; barriers and facilitators affecting health personnel capacity; human and ergonomic factors; separation and personal protective equipment (PPE), fatigue due to isolation and PPE?)

37

Clinical management

*Evaluation of the disease progression and disease consequences in specific groups (pregnant mothers, children, the elderly, etc.)

38

Social science, public health and participation in responding to public health and clinical research

*Multidisciplinary and interdisciplinary interventions, randomized control trials (RCTs) in developing behaviours and learning prevention strategies

39

Clinical management

Studies related to the range of manifestations and the clinical profiles of patients in mild and severe cases of the disease

40

Clinical management

*Evaluation of nosocomial infections and disease transmission in hospitals and methods to reduce this type of infection in hospitals

41

Epidemiology

What are the environmental conditions associated with the increased likelihood of transmission (e.g. temperature, humidity, seasonal conditions)? *Accurate study of the impact of weather on disease transmission mainly at the meso and micro level, research on the impact of temperature on the eradication of the disease

42

Infection control

What are the risk factors for virus transmission and disease outbreak among healthcare workers?

43

Social science, public health and participation in responding to public health and clinical research

*Socioeconomic factors affecting the control, infection and treatment of COVID-19 and the impact of sociocultural factors on the global COVID-19 challenge

44

Clinical management

*Statistical modelling and determining the correct method of analysing the information recorded in hospitals in terms of disease consequences

45

Clinical management

*The study of the clinical characteristics, severity and the progression of the disease in specific patients (cardiovascular patients, organ transplants, diabetes, cancers, chronic respiratory diseases, AIDS, immunosuppression, chronic kidney diseases, etc.) at the national and provincial levels

46

Social science, public health and participation in responding to public health and clinical research

*Build an app for people that takes into account the psychological dimensions for suspicious people and others (currently, everyone wants to have a CT scan and COVID test, while it is not really needed)

47

Epidemiology

*Modelling to determine the time of the end of crisis (When will the wards return to their original state? What is the prediction for the unforeseen sudden crisis?) Predicting the course of the epidemic and its trend/using intelligent methods to predict the epidemiological indicators of the disease

48

Epidemiology

*Futuristic models for identifying the needed interventions and preparedness for different epidemic conditions

49

Epidemiology

What is the cause of epidemiological time delays (for example, from the onset of symptoms to the diagnosis of the disease, the onset of symptoms to hospitalization), and what effect do these delays have on epidemic doubling time?

50

Ethics

*Case study of the moral manifestations of the health community in the COVID-19 epidemic

51

Infection control

How important are separation, quarantine and ideal processes in medical care? Co-separation in front of single rooms; costs and resources for co-separation, criteria, principles and cost-effectiveness of quarantine; unintended consequences of quarantine and isolation. Medical care processes and access to responsive health services to minimize contacts

52

Vaccine R&D

*The impact of genetic factors and various interleukins on COVID-19 disease in order to make drugs and vaccines specific to the Iranian population by using the country’s existing bio-banks

53

Infection control

Identifying the importance of PPE and IPC measures and the relative importance of special PPE/IPC measures, type of the mask and eye protection; is it necessary to take precautions against airborne droplets in certain environments (regular care against aerosol production methods), PPE for triage, spatial separation with optimal distance? Comparison of the quality and results of personnel prevention tools (masks, disinfection, clothing, guns, separation, etc.) and their results in different hospitals, reviewing different methods of protecting personnel and the results of such measures in hospitals

54

Epidemiology

Evaluation of susceptibility, infection and the severity of COVID-19 infection in non-COVID-19 patients (all cases of the hospitalized or non-hospitalized populations)

55

Virology, transmission, diagnosis

How can technical deficiencies such as simple immunofluorescence antibody assay (IFA), differential IFA, enzyme-linked immunosorbent assay (ELISA), neutralization assay, substitute neutralization methods including false types and competitive ELISA be addressed?

56

Social science

Assessing people’s views on traditional medicine methods introduced during the COVID-19 disease crisis

57

Epidemiology

What is the relative importance of the virus transmission in asymptomatic or pre-symptomatic individuals? Is there a transmission, and what is its impact? Can asymptomatic vectors transmit the virus? *Assessing the frequency of asymptomatic individuals, retrospective screening of patients for accurate and individualized recording of the mode of disease transmission, assessing the rate of virus transmission in families (father–child, wife–husband, mother–child, brother–sister, identical twins in comparison with fraternal, etc.)

58

Epidemiology

*Using mathematical modelling and determining high-risk groups by using neural network methods and other mathematical models

59

Virology, transmission, diagnosis

What are the tests that determine the point of care (care testing)?

60

Virology, transmission, diagnosis

Identifying methods for diagnosing diagnostic drift (PCR compatibility may change over time due to mutations in probe or primer-binding sites)

61

Virology, transmission, diagnosis

Identification of escape mutants (in the laboratory) and genotypic–phenotypic approaches (to monitor treatment). It is suggested that sequences be prepared from samples of patients from different ages in different phases of the disease [mild, moderate, severe, acute respiratory distress syndrome (ARDS) and deceased patients] and try to investigate the possible relationship between the occurrence of mutations and these phases and finally draw conclusions. Criteria for sample selection and evaluation are listed in separate instructions

62

Epidemiology

Does the infection produce neutralizing antibodies? Are there any antibody-dependent (vaccine) strategies to fight the disease and infection?

63

Virology, transmission, diagnosis

What are the reliable methods for measuring antibodies?

64

Epidemiology

What is the impact of PPE and measures such as maintaining social distancing and wearing a face mask?

65

Virology, transmission, diagnosis

What is the relationship between genetic indicators and reduced phenotypic sensitivity to specific antivirals (more information on virus and host characteristics is needed to predict virus traits or disease severity)

66

Virology, transmission, diagnosis

Are immune indicators related to the prognosis of the disease?

67

Virology, transmission, diagnosis

What are the digital solutions to help the field lab?

68

Virology, transmission, diagnosis

Can cellular immunogenicity be measured with cell-surface substitutes [enzyme-linked immune absorbent spot (ELISpot), etc.]?

69

Epidemiology

What are the causes and conditions that increase the power of transmission? What is their contribution to the spread of the disease?

70

Clinical management

*The studies whose response to preparing nutrition guidelines (what foods boost the immune system) for specific conditions, such as immunodeficient patients and ICU patients, and guidelines for caring for pregnant mothers, including the needed training, diagnosis, determining the necessary visits and determining the necessary ultrasounds to reduce the number of visits, psychiatric counselling and follow-up

71

Infectious control

Identifying transmission methods and transmission duration (which affect the selection of the most appropriate IPC measures and their optimal duration)

72

Virology, transmission, diagnosis

How can the loss of assessing efficiency due to mutations be prevented? This is true of commercially manufactured kits that may not be compatible with intra-organizational PCR speeds and may emit fewer starter/prober sequences. This threat is minimized by developing PCR methods that target protected areas that are relatively stable

73

Epidemiology

Are children less susceptible to COVID-19? If so, why? If they are susceptible but asymptomatic, are they vectors of the virus? Do they transmit the virus?

74

Virology, transmission, diagnosis

What are the sequencing approaches on the patient's bedside and laboratory?

75

Infectious control

Identifying the environmental stability of the virus and effective methods to minimize the role of the environment in its transmission

76

Infectious control

Survival of the virus on surfaces and factors affecting the stability of the virus (e.g. surface type, humidity, temperature, the amount of protein). The effectiveness of various disinfectants for cleaning surfaces around the patient, including the extensive range used in different situations (cleaning body fluids versus regular surface cleaning) and in environments with different levels of resources used

77

Virology, transmission, diagnosis

What technologies should be developed to identify prognostic indicators?

78

Virology, transmission, diagnosis

Can serological specificity and co-stimulation or serological cross-reactivity add value to serological diagnosis?

79

Virology, transmission, diagnosis

Is viral load or viral load pathway (viral load trajectories) related to disease prognosis (knowing this relationship is necessary to create a profile of disease severity)? Due to the lack of quantitative kits on the market at this time, cycle of threshold (Ct) analysis in real-time PCR tests should be the criterion for evaluation

80

Infectious control

*Evaluation of waste management and infectious waste in COVID-19 hospitals

81

Infectious control

*Preparation of evidence-based guidelines for infection control in hospitals (for example, the difference between the persistence of the virus on metal and plastic and its use in hospitals), preparation of personnel protection protocol

82

Virology, transmission, diagnosis

Are there any possible methods for detecting multiple respiratory pathogens?

83

Epidemiology

*Does innate immunity in this disease make sense? That is, can we assume that a percentage of the population, even if they have effective contact, have no chance of infection, or it is very low? What is the nature of this immunity (genetics or cross-immunity with other microorganisms and even other vaccines, etc.)

84

Virology, transmission, diagnosis

What indicators determine the infectivity of the disease (such as discharge-related criteria, and how much the viral load in the upper respiratory tract versus the lower respiratory tract can be a reliable alternative indicator for this purpose)?

85

Infectious control

*Is spraying of disinfectants at the entrances of hospitals and offices effective in eliminating the COVID-19 virus? Which disinfectant and with what density and when is effective?

86

Vaccine R&D

While there is a good understanding of what should be done in a clinical trial at an early stage, fundamental decisions need to be made about the design of clinical trials at a later stage

87

Virology, transmission, diagnosis

Is there an innate immunization in these viruses?

88

Clinical management

Viral kinetic study and pathophysiology of severe COVID-19 disease

89

Infectious control

Identifying all target tissues for virus entry, identifying all body fluids that contain the virus and can transmit the virus (RNA detection against live virus and determination of viral load), importance of airborne transmission and “opportunistic airborne” spread and vertical transmission. The duration of spread and the probability of asymptomatic spread; the ability of the virus to transmit to others through asymptomatic transmission and, if proven, the relative frequency of such transmission events

90

Infectious control

Provide services securely. Electronic monitoring of syndromic signatures of people under supervision and care at home and patients in isolation (e.g. the use of point-of-care sensors and wearable monitoring and artificial intelligence support)

91