Prospective Cohort Study

admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

As the world's attention has been riveted upon the growing COVID-19 pandemic, many researchers have written brief reports supporting the hypothesis that vitamin D deficiency is related to the incidence and severity of COVID-19. The clear common thread among the top risk groups-vitamin D deficiency-may be being overlooked because of previous overstated claims of vitamin D benefits. However, the need to decrease COVID-19 fatalities among high-risk populations is urgent. Early researchers reported three striking patterns. Firstly, the innate immune system is impaired by vitamin D deficiency, which would predispose sufferers to viral infections such as COVID-19. Vitamin D deficiency also increases the activity of the X-chromosome-linked "Renin-Angiotensin" System, making vitamin D deficient individuals (especially men) more susceptible to COVID-19's deadly "cytokine storm" (dramatic immune system overreaction). Secondly, the groups who are at highest risk for severe COVID-19 match those who are at highest risk for severe vitamin D deficiency. This includes the elderly, men, ethnic groups whose skin is naturally rich in melanin (if living outside the tropics), those who avoid sun exposure for cultural and health reasons, those who live in institutions, the obese, and/or those who suffer with hypertension, cardiovascular disease, or diabetes. And thirdly, the pattern of geographical spread of COVID-19 reflects higher population vitamin D deficiency. Both within the USA and throughout the world, COVID-19 fatality rates parallel vitamin D deficiency rates. A literature search was performed on PubMed, Google Scholar, and RSMLDS, with targeted Google searches providing additional sources. Although randomized controlled trial results may be available eventually, the correlational and causal study evidence supporting a link between vitamin D deficiency and COVID-19 risks is already so strong that it supports action. The 141 author groups writing primarily about biological plausibility detailed how vitamin D deficiency can explain every risk factor and every complication of COVID-19, but agreed that other factors are undoubtedly at work. COVID-19 was compared with dengue fever, for which oral vitamin D supplements of 4,000 IU for 10 days were significantly more effective than 1,000 IU in reducing virus replication and controlling the "cytokine storm" (dramatic immune system over-reaction) responsible for fatalities. Among the 47 original research studies summarized here, chart reviews found that serum vitamin D levels predicted COVID-19 mortality rates (16 studies) and linearly predicted COVID-19 illness severity (8 studies). Two causal modeling studies and several analyses of variance strongly supported the hypothesis that vitamin D deficiency is a causal, rather than a bystander, factor in COVID-19 outcomes. Three of the four studies whose findings opposed the hypothesis relied upon disproven assumptions. The literature review also found that prophylactically correcting possible vitamin D deficiency during the COVID-19 pandemic is extremely safe. Widely recommending 2,000 IU of vitamin D daily for all populations with limited ability to manufacture vitamin D from the sun has virtually no potential for harm and is reasonably likely to save many lives.

/pdf/a-basic-review-of-the-preliminary-evidence-that-covid-19-31kw3u2yta.pdf

A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency

Improved understanding of the effects of meteorological conditions on the transmission of SARS-CoV-2, the causative agent for COVID-19 disease, is needed. Here, we estimate the relationship between air temperature, specific humidity, and ultraviolet radiation and SARS-CoV-2 transmission in 2669 U.S. counties with abundant reported cases from March 15 to December 31, 2020. Specifically, we quantify the associations of daily mean temperature, specific humidity, and ultraviolet radiation with daily estimates of the SARS-CoV-2 reproduction number (Rt) and calculate the fraction of Rt attributable to these meteorological conditions. Lower air temperature (within the 20-40 °C range), lower specific humidity, and lower ultraviolet radiation were significantly associated with increased Rt. The fraction of Rt attributable to temperature, specific humidity, and ultraviolet radiation were 3.73% (95% empirical confidence interval [eCI]: 3.66-3.76%), 9.35% (95% eCI: 9.27-9.39%), and 4.44% (95% eCI: 4.38-4.47%), respectively. In total, 17.5% of Rt was attributable to meteorological factors. The fractions attributable to meteorological factors generally were higher in northern counties than in southern counties. Our findings indicate that cold and dry weather and low levels of ultraviolet radiation are moderately associated with increased SARS-CoV-2 transmissibility, with humidity playing the largest role.

/pdf/role-of-meteorological-factors-in-the-transmission-of-sars-4gs4666bkx.pdf

Role of meteorological factors in the transmission of SARS-CoV-2 in the United States.

Vitamin D is a hormone that acts on many genes expressed by immune cells. Evidence linking vitamin D deficiency with COVID-19 severity is circumstantial but considerable-links with ethnicity, obesity, institutionalization; latitude and ultraviolet exposure; increased lung damage in experimental models; associations with COVID-19 severity in hospitalized patients. Vitamin D deficiency is common but readily preventable by supplementation that is very safe and cheap. A target blood level of at least 50 nmol l-1, as indicated by the US National Academy of Medicine and by the European Food Safety Authority, is supported by evidence. This would require supplementation with 800 IU/day (not 400 IU/day as currently recommended in UK) to bring most people up to target. Randomized placebo-controlled trials of vitamin D in the community are unlikely to complete until spring 2021-although we note the positive results from Spain of a randomized trial of 25-hydroxyvitamin D3 (25(OH)D3 or calcifediol) in hospitalized patients. We urge UK and other governments to recommend vitamin D supplementation at 800-1000 IU/day for all, making it clear that this is to help optimize immune health and not solely for bone and muscle health. This should be mandated for prescription in care homes, prisons and other institutions where people are likely to have been indoors for much of the summer. Adults likely to be deficient should consider taking a higher dose, e.g. 4000 IU/day for the first four weeks before reducing to 800 IU-1000 IU/day. People admitted to the hospital with COVID-19 should have their vitamin D status checked and/or supplemented and consideration should be given to testing high-dose calcifediol in the RECOVERY trial. We feel this should be pursued with great urgency. Vitamin D levels in the UK will be falling from October onwards as we head into winter. There seems nothing to lose and potentially much to gain.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.201912

Vitamin D and COVID-19: evidence and recommendations for supplementation

Prior studies indicate the protective role of Ultraviolet-B (UVB) radiation in human health, mediated by vitamin D synthesis. In this observational study, we empirically outline a negative association of UVB radiation as measured by ultraviolet index (UVI) with the number of COVID-19 deaths. We apply a fixed-effect log-linear regression model to a panel dataset of 152 countries over 108 days (n = 6524). We use the cumulative number of COVID-19 deaths and case-fatality rate (CFR) as the main dependent variables and isolate the UVI effect from potential confounding factors. After controlling for time-constant and time-varying factors, we find that a permanent unit increase in UVI is associated with a 1.2 percentage points decline in daily growth rates of cumulative COVID-19 deaths [p < 0.01] and a 1.0 percentage points decline in the CFR daily growth rate [p < 0.05]. These results represent a significant percentage reduction in terms of daily growth rates of cumulative COVID-19 deaths (− 12%) and CFR (− 38%). We find a significant negative association between UVI and COVID-19 deaths, indicating evidence of the protective role of UVB in mitigating COVID-19 deaths. If confirmed via clinical studies, then the possibility of mitigating COVID-19 deaths via sensible sunlight exposure or vitamin D intervention would be very attractive.

/pdf/evidence-of-protective-role-of-ultraviolet-b-uvb-radiation-2cifbq2tre.pdf

Evidence of protective role of Ultraviolet-B (UVB) radiation in reducing COVID-19 deaths.

Background: Research is ongoing to identify an effective way to prevent or treat COVID-19, but thus far these efforts have not yet identified a possible solution. Prior studies indicate the protective role of Ultraviolet-B (UVB) radiation in human health, mediated by vitamin D synthesis. In this study, we empirically outline a negative association of UVB radiation as measured by ultraviolet index (UVI) with the number of deaths attributed to COVID-19 (COVID-19 deaths).

Methods: We carry out an observational study, applying a fixed-effect log-linear regression model to a panel dataset of 152 countries over a period of 108 days (n=6524). We use the cumulative number of COVID-19 deaths and case-fatality rate (CFR) as the main dependent variables to test our hypothesis and isolate UVI effect from potential confounding factors such as underlying time trends, country-specific time-constant and time-varying factors such as weather.

Findings: After controlling for time-constant and time-varying factors, we find that a permanent unit increase in UVI is associated with a 1.2 percentage points decline in daily growth rates of cumulative COVID-19 deaths [p < 0.01] as well as a 1.0 percentage points decline in the daily growth rates of CFR [p < 0.05]. These results represent a significant percentage reduction in terms of the daily growth rates of cumulative COVID-19 deaths (-11.88%) and CFR (-38.46%). Our results are consistent across different model specifications.

Interpretation: We find a significant negative association between UVI and COVID-19 deaths, indicating evidence of the protective role of UVB in mitigating COVID-19 deaths. If confirmed via clinical studies, then the possibility of mitigating COVID-19 deaths via sensible sunlight exposure or vitamin D intervention will be very attractive because it is cost-effective and widely available.

/pdf/evidence-of-protective-role-of-ultraviolet-b-uvb-radiation-4u49jggnw3.pdf

Evidence of Protective Role of Ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths

Background Nations are imposing unprecedented measures at large-scale to contain the spread of COVID-19 pandemic. Recent studies indicate that measures such as lockdowns may have slowed down the growth of COVID-19. However, in addition to substantial economic and social costs, these measures also limit the exposure to Ultraviolet-B radiation (UVB). Emerging observational evidence indicate the protective role of UVB and vitamin D in reducing the severity and mortality of COVID-19 deaths. In this observational study, we empirically outline the independent protective roles of lockdown and UVB exposure as measured by ultraviolet index (UVI), whilst also examining whether the severity of lockdown is associated with a reduction in the protective role. Methods We apply a log-linear fixed-effects model to a panel dataset of 162 countries over a period of 108 days (n=6049). We use the cumulative number of COVID-19 deaths as the dependent variable and isolate the mitigating influence of lockdown severity on the association between UVI and growth-rates of COVID-19 deaths from time-constant country-specific and time-varying country-specific potentially confounding factors. Findings After controlling for time-constant and time-varying factors, we find that a unit increase in UVI and lockdown severity are independently associated with 17% [-1.8 percentage points] and 77% [-7.9 percentage points] decline in COVID-19 deaths growth rate, indicating their respective protective roles. However, the widely utilized and least severe lockdown (recommendation to not leave the house) already fully mitigates the protective role of UVI by 95% [1.8 percentage points] indicating its downside. Interpretation We find that lockdown severity and UVI are independently associated with a slowdown in the daily growth rates of cumulative COVID-19 deaths. However, we find consistent evidence that increase in lockdown severity is associated with a significant reduction in the protective role of UVI in reducing COVID-19 deaths. Our results suggest that lockdowns in conjunction with adequate exposure to UVB radiation might have provided even more substantial health benefits, than lockdowns alone. For example, we estimate that there would be 21% fewer deaths on average with sufficient UVB exposure while people were recommended not to leave their house. Therefore, our study outlines the importance of considering UVB exposure, especially while implementing lockdowns and may support policy decision making in countries imposing such measures.

/pdf/does-lockdown-decrease-the-protective-role-of-ultraviolet-b-2e1rlgqywz.pdf

Does Lockdown Decrease the Protective Role of ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths?

Background: Brazil reported 123,780 deaths across 27 administrative regions, making it the second-worst affected country after the US in terms of COVID-19 deaths as of 3 September 2020. Understanding the role of weather factors in COVID-19 in Brazil is helpful in the long-term mitigation strategy of COVID-19 in other tropical countries because Brazil experienced early large-scale outbreak among tropical countries. Recent COVID-19 studies indicate that relevant weather factors such as temperature, humidity, UV Index (UVI), precipitation, ozone, pollution and cloud cover may influence the spread of COVID-19. Yet, the magnitude and direction of those associations remain inconclusive. Furthermore, there is only limited research exploring the impact of these weather factors in a tropical country like Brazil. In this observational study, we outline the roles of 7 relevant weather factors including temperature, humidity, UVI, precipitation, ozone, pollution (visibility) and cloud cover in COVID-19 deaths in Brazil.
Methods: We use a log-linear fixed-effects model to a panel dataset of 27 administrative regions in Brazil across 182 days (n=3882) and analyze the role of relevant weather factors by using daily cumulative COVID-19 deaths in Brazil as the dependent variable. We carry out robustness checks using case-fatality-rate (CFR) as the dependent variable. 
Findings: We control for all time-fixed and various time-varying region-specific factors confounding factors. We observe a significant negative association of COVID-19 daily deaths growth rate in Brazil with weather factors - UVI, temperature, ozone and cloud cover. Specifically, a unit increase in UVI, maximum temperature, and ozone independently associate with 6.0 percentage points [p<0.001], 1.8 percentage points [p<0.01] and 0.3 percentage points [p<0. 1] decline in COVID-19 deaths growth rate. Further, a unit percentage increase in cloud cover associates with a decline of 0.148 percentage points [p<0.05] in COVID-19 deaths growth rate. Surprisingly, contrary to other studies, we do not find evidence of any association between COVID-19 daily deaths growth rate and humidity, visibility and precipitation. We find our results to be consistent even when we use the CFR as the dependent variable.
Interpretation: We find independent protective roles of UVI, temperature, ozone and cloud cover in mitigating COVID-19 deaths, even in a tropical country like Brazil. We observe these results to be consistent across various model specifications, especially for UVI and cloud cover, even after incorporating additional time-varying weather parameters such as dewpoint, pressure, wind speed and wind gust. These results could guide health-related policy decision making in Brazil as well as similar tropical countries.

/pdf/role-of-weather-factors-in-covid-19-death-growth-rates-in-3thdwhbmfk.pdf

Role of Weather Factors in COVID-19 Death Growth Rates in Tropical Climate: A Data-Driven Study Focused on Brazil Manuscript

Background. Prior studies indicate the protective role of Ultraviolet-B (UVB) radiation in human health, mediated by vitamin D synthesis. In this observational study, we empirically outline a negative association of UVB radiation as measured by ultraviolet index (UVI) with the number of COVID-19 deaths.

Methods. We apply a fixed-effect log-linear regression model to a panel dataset of 152 countries over 108 days (n=6524). We use the cumulative number of COVID-19 deaths and case-fatality rate (CFR) as the main dependent variables and isolate the UVI effect from potential confounding factors.

Findings. After controlling for time-constant and time-varying factors, we find that a permanent unit increase in UVI is associated with a 1.2 percentage points decline in daily growth rates of cumulative COVID-19 deaths [p < 0.01] and a 1.0 percentage points decline in the CFR daily growth rate [p < 0.05]. These results represent a significant percentage reduction in terms of daily growth rates of cumulative COVID-19 deaths (-12%) and CFR (-38%).

Interpretation. We find a significant negative association between UVI and COVID-19 deaths, indicating evidence of the protective role of UVB in mitigating COVID-19 deaths. If confirmed via clinical studies, then the possibility of mitigating COVID-19 deaths via sensible sunlight exposure or vitamin D intervention would be very attractive.

Rahul Kalippurayil Moozhipurath

Papers

Evidence of protective role of Ultraviolet-B (UVB) radiation in reducing COVID-19 deaths.

Evidence of Protective Role of Ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths

Does Lockdown Decrease the Protective Role of ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths?

Role of Weather Factors in COVID-19 Death Growth Rates in Tropical Climate: A Data-Driven Study Focused on Brazil Manuscript

Evidence of Protective Role of Ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths