Covid-19, Respiratory Tract Infections
Conditions
Keywords
Cod liver oil, Vitamin D, n-3 LCPUFAs, SARS-CoV virus
Brief summary
A randomized, parallel-group treatment, quadruple masked, two-arm study to assess the effectiveness of cod liver oil compared to placebo in the prevention of Covid-19 and airway infections in healthy adults. In this study, the investigators will investigate whether daily cod liver oil can prevent Covid-19 infections and reduce the severity of such infections. The investigators will also examine whether cod liver oil prevents other airway infections in healthy adults.
Detailed description
Preliminary evidence from literature and an ongoing study in the investigators' lab suggests that cod liver oil may prevent Covid-19 and complications of Covid-19. In the present study, the investigators will examine whether this is actually the case by randomizing volunteers to take cod liver oil or placebo (corn oil) during the winter months of 2020-2021. The investigators also aim to explore whether cod liver oil can prevent other respiratory tract infections, as well as explore and confirm already known health effects and possible new health effects, in particular rare adverse events associated with cod liver oil use. Cod liver oil is a traditional source of vitamin A, D, and E and omega-3 fatty acids and the dose administered in the study will contain 250 ug vitamin A, 10 ug vitamin D, 10 mg vitamin E, and 1,2 g omega-3 fatty acids.
Interventions
DIETARY_SUPPLEMENTCod liver oil
5 ml of cod liver oil as a source of 10 ug of vitamin D and 1.2 g of long-chained n-3 polyunsaturated fatty acids (DHA 0,6g and EPA 0,4g) per day for 6 months x 1 time/day together with the first meal of the day. 5ml of Cod liver oil also contains 250ug vitamin A and 10 mg vitamin E.
DIETARY_SUPPLEMENTCorn oil (placebo)
5 ml of corn oil per day for 6 months x 1 time/day together with the first meal of the day
Sponsors
University of Oslo
Norwegian Institute of Public Health
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, investigators, care providers, data collectors, outcomes assessors, and data analysts will be masked to the group assignment of each participant. Unmasking will be done after analysis of all primary endpoints and, preferably, also all secondary endpoints are completed. After unmasking the unmasked list will only be made available to study personnel needing this for conducting their tasks.
Intervention model description
A parallel-group treatment, two-arm study where participants are randomly assigned to cod liver oil or placebo (corn oil) in a 1:1 ratio
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Any person \>18 years with a Norwegian Personal Identity Number
Exclusion criteria
* History of renal failure or dialysis, hypercalcemia, severe liver disease (cirrhosis), sarcoidosis or other granulomatous diseases (Wegener) * Allergy to fish or corn oil. * Pregnancy or planned pregnancy before summer 2021 * Vegan diet * Age \>75 years old at inclusion based on the Norwegian Personal Identity Number * Difficulty in swallowing cod liver oil or other oils * Previous Covid-19 disease * For Caucasians only: Use of any supplement containing more than trace amounts of vitamin D or omega-3 fatty acids at inclusion (Vitamin D levels in non-Caucasians living in Norway are frequently low even among those self-reporting using dietary supplements). This criterion will be relaxed if too few participants volunteer for the study and only Caucasians that use cod liver oil or an equivalent dietary supplement (with omega 3 and vitamin D) more than 5-7 times per week will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants diagnosed with serious Covid-19 | 6 months | The number of participants with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories in the period from one week after the start of cod liver oil/placebo taking to the end of this period together with any of the following: A) Self-reported dyspnea and fever concurrent (within four weeks) with the positive test OR B) hospitalization caused by Covid-19 concurrent (within four weeks) with the positive test OR C) death where the Covid-19 infection was wholly or partly responsible as judged by the death certificate (see endpoint in the protocol) |
| Number of participants diagnosed with New Covid-19 | 6 months | The number of participants diagnosed with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories from one week after the start of cod liver oil/placebo taking. |
| Number of participants with negative SARS-CoV-2 test | 6 months | Number of participants with an airway sample negative for SARS-CoV-2 (indicative of another airway infection). \*Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories. |
| Number of participants with self-reported airway infection | 6 months | The number of episodes with any two of the following symptoms: fever, cough, nasal congestion or sore throat |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of visits at GP for infections | 6 months | Based on The Norwegian Reimbursement Database |
| Number of participants hospitalized due to Covid-19 | 6 months | Number of participants hospitalized wholly or partly caused by Covid-19. |
| Number of visits at GP | 6 months | Based on The Norwegian Reimbursement Database |
| Number of participants in Intensiv Care Unit (ICU) caused by Covid-19 | 6 months | Number of participants with ICU care wholly or partly caused by Covid-19. |
| Number of participants with any admissions to hospital | 6 months | Number of participants with any admissions to hospital based on the Norwegian Patient Registry data. |
| Infection with each of the mentioned pathogens | 6 months | An airway sample positive for a respiratory pathogen\* (either PCR or culture) in the period from one week after the start of cod liver oil/placebo taking to the end of this period. \*Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Self-reported airway infection | 12 months | The number of episodes with any two of the following symptoms: fever, cough, nasal congestion or sore throat |
| Incidence of Cardiovascular disease | 6 months | Based on self-reporting and Norwegian Registries |
| Number of participants with cod liver oil related adverse events | 12 months | Number of participants hospitalized for major diseases or death in the cod liver oil versus placebo group in Norwegian registries |
| Number of participants with self-reported cod liver oil related adverse events | 12 months | Number of participants with self-reported adverse events |
| Incidence of cardiovascular mortality | 6 months | Based on self-reporting and Norwegian Registries |
| Incidence of cancer | 6 months | Based on self-reporting and Norwegian Registries |
| Incidence of cancer mortality | 6 months | Based on self-reporting and Norwegian Registries |
| All-cause mortality | 6 months | Based on self-reporting and Norwegian Registries |
| Incidence of fracture of the hip or forearm | 6 months | Based on self-reporting and Norwegian Registries |
| Incident dementia | 6 months | Based on self-reporting and Norwegian Registries |
| Number of participants diagnosed with serious Covid-19 | 12 months | The number of participants with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories in the period from one week after the start of cod liver oil/placebo taking to the end of this period together with any of the following: A) Self-reported dyspnea and fever concurrent (within four weeks) with the positive test OR B) hospitalization caused by Covid-19 concurrent (within four weeks) with the positive test OR C) death where the Covid-19 infection was wholly or partly responsible as judged by the death certificate (see endpoint in the protocol) |
| Number of participants diagnosed with new Covid-19 | 12 months | The number of participants diagnosed with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories from one week after the start of cod liver oil/placebo taking. |
| Laboratory confirmed respiratory tract infection | 12 months | An airway sample positive for a respiratory pathogen\* (either PCR or culture). \*Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories. |
Countries
Norway
Outcome results
None listed