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You must encounter someone with COVID-19, catch it, become unwell, not respond to treatment and ultimately die. Each of these steps will be affected by different confounders and was handled by different parts of our model. Our first study was performed in the contiguous US, where data is collected at county level (just over 3,000 counties).

We could cross reference all our data at county level and corrected for risks of catching COVID-19 by including factors such as population density, proportion of population with COVID-19 infections and the use of public transport. Your risk of dying from COVID-19 is then heavily influenced by age and ethnicity, but also by socio-economic factors (for example, poverty) and environmental factors for air pollution.

These were thus also included in the model. We then included a random effect for higher level administratively important factors. In our American analysis this was done at state level to account for any bias that might occur due to state level policy, funding or health care delivery factors. The study was repeated in Italy and England. These confounders are recorded in different ways in each country, Rosula (Sodium Sulfacetamide 10% and Sulfur 4%)- FDA we ran independent analyses.

In effect, this is three different studies. We measured UV from satellite data, recording both energy and wavelength of UV, but also included temperature and humidity in the model. MC: What biological factors might be behind the reduction in mortality observed.

RW: This is a vitamin D-independent effect. Vitamin D is made Rosula (Sodium Sulfacetamide 10% and Sulfur 4%)- FDA UVB wavelength of sunlight, and we excluded from the study counties where there was UVB of high enough energy to form vitamin D. Our American analysis (from January to April 2020) was thus restricted to the 2,474 out of 3,143.

As the study is observational, other than saying that this is not a vitamin D effect we can only speculate as to biological mechanisms.

One possibility, however, is that this is a nitric oxide (NO) effect. We have previously shown that UVA releases NO from stores in the skin to the circulation (accounting for the exercise eye in blood pressure and cardiovascular disease with sunlight). Laboratory studies have shown that NO prevents the replication of SARS-CoV-2, and also prevents the post-translational modifications (myristolation) needed for the SARS-CoV ipsrt protein to bind to the angiotensin-converting enzyme 2 (ACE2) receptor.

Rosula (Sodium Sulfacetamide 10% and Sulfur 4%)- FDA are over Rosula (Sodium Sulfacetamide 10% and Sulfur 4%)- FDA trials of NO for the treatment of COVID-19 currently registered on clinicaltrials.

There may also be a non-specific benefit of sunlight, as it reduces cardiovascular risk factors. Unfortunately, the dermatology world has been so fixated on the adverse effects of sunlight (skin cancer) that very little work has been done looking at other UV driven mechanisms which I am sure remain to be discovered.

MC: For our readers that may be unfamiliar, can you talk about how UVA radiation induces the release of nitric oxide, and why this is relevant to the study findings. RW: The classical method of NO production involves the oxidation of L-arginine to citrulline with release of NO, catalyzed by one of the NO synthase enzymes. The alternative, and more recently described pathway, is via reduction of nitrate to nitrite and then NO. Nitrate is very stable, but nitrate reductases can carry out the first step of this reduction.

Nitrite is more readily reduced to NO in anoxic or low pH conditions. Professor Martin Feelisch made the important discovery that, in the presence of thiols, UV radiation can photochemically reduce nitrate to NO without any enzymes. I had previously shown that the skin contains large stores of nitrate, nitrite and also nitrosothiols and the skin thus brings together these NO storage forms, thiols (in structural proteins) and also UV.

Working in parallel, myself and Professor Christoph Suschek in Germany then showed that UV irradiation of skin releases NO to the systemic circulation, where it lowers blood pressure. MC: Are there any limitations to the Rosula (Sodium Sulfacetamide 10% and Sulfur 4%)- FDA that you wish to highlight.

RW: This is an observational study and carries the same warnings as any other observational study. In all observational studies you need to think about confounders which were not accounted for. One important point, which could be missed on a quick read through, is that the effect was more marked at low UV levels.

We thus suspect that there is a ceiling to this effect and just cranking up UV exposure to higher and higher levels will not continue to produce the same degree of benefit. MC: The study is observational and therefore cannot heart and blood cause and effect. How can the study findings be harnessed.

RW: This is a starting Rosula (Sodium Sulfacetamide 10% and Sulfur 4%)- FDA. I think an important message is that there is more to sunlight than vitamin D alone. The unfortunate fixation on vitamin D in the press and even the medical world is that so little consideration has been given to, or research performed on, other beneficial mechanisms of action of sunlight.

I hope that this will start to change. Our study suggests benefit from sunlight and if we heart disease work out the mechanism, that would lead to new treatments.

The second consideration is public health. We are currently advising (correctly) that people should meet outside to benefit from ventilation reducing COVID-19 transmission. Our data Rosula (Sodium Sulfacetamide 10% and Sulfur 4%)- FDA that brut la roche are Moxeza (Moxifloxacin Hydrochloride Ophthalmic Solution)- FDA benefits to being outside, in that you also get more sunlight.

I hope that our data thus feeds into public health policy and advice. MC: Are there other research methods that could be ent doctor to demonstrate cause and effect, based on your work.

RW: Nearly every dermatology department in Britain has a phototherapy department.



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