Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10−8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice. A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

/pdf/genetic-mechanisms-of-critical-illness-in-covid-19-16rr9c938j.pdf

Genetic mechanisms of critical illness in Covid-19.

Low-level laser (light) therapy (LLLT) is a fast-growing technology used to treat a multitude of conditions that require stimulation of healing, relief of pain and inflammation, and restoration of function. Although the skin is the organ that is naturally exposed to light more than any other organ, it still responds well to red and near-infrared wavelengths. The photons are absorbed by mitochondrial chromophores in skin cells. Consequently electron transport, adenosine triphosphate (ATP) nitric oxide release, blood flow, reactive oxygen species increase and diverse signaling pathways get activated. Stem cells can be activated allowing increased tissue repair and healing. In dermatology, LLLT has beneficial effects on wrinkles, acne scars, hypertrophic scars, and healing of burns. LLLT can reduce UV damage both as a treatment and as a prophylaxis. In pigmentary disorders such as vitiligo, LLLT can increase pigmentation by stimulating melanocyte proliferation and reduce depigmentation by inhibiting autoimmunity. Inflammatory diseases such as psoriasis and acne can also benefit. The non-invasive nature and almost complete absence of side-effects encourages further testing in dermatology.

Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring.

BASAL-CELL and squamous-cell cancers of the skin are the most frequent malignant conditions in the white population. About 600,000 new cases are detected each year in the United States.1 Fortunately, only a small proportion lead to death. Nonmelanoma cancers are associated with substantial morbidity, including loss of function and disfigurement, and their treatment is costly. Early detection can reduce morbidity and cost. We will review the epidemiology, recognition, treatment, and prevention of basal-cell and squamous-cell carcinomas, which together account for most nonmelanoma skin cancers (we exclude tumors of the mucous membranes). We shall emphasize risk factors for the development of . . .

Nonmelanoma Cancers of the Skin

Laser-tissue interactions

https://iopscience.iop.org/article/10.1088/0031-9155/35/9/001/pdf

Physics of thermal processes in laser-tissue interaction

The values for the maximum coagulation depth (MCD) of various types of lasers which are specified in the literature are not comparable, because often different irradiation times were used. MCD depends not only on the wavelength of laser light, but also on the time of action of the laser beam, because of heat transfer. In excised human skin MCD was determined histologically for irradiation with the argon laser, Nd:YAG laser, and CO2 laser. Extending the irradiation time from 0.2 s to 10 s results in a 4-6-fold increase in MCD. Coagulation experiments performed with a soldering iron have shown results similar to those obtained with the CO2 laser. Enlargement of the laser-beam diameter from 1 to 2 mm leads to a 50% increase in MCD. Additional chilling of the skin with water during laser irradiation protects the skin from evaporation, and the values for MCD increase to 3.5 mm for the argon laser and 5.5 mm for Nd:YAG laser. Detailed knowledge of the MCD is necessary to obtain the desired therapeutic effect, and also to avoid unwanted effects.

Comparison of the maximum coagulation depth in human skin for different types of medical lasers.

Three patients with port-wine stains with a nodular surface, one patient with macrocheilia resulting from a port-wine stain, and one patient with a capillary hemangioma were treated with a Nd-YAG laser (mediLas, MBB-AT, Munich). Irradiance was between 800 and 1,600 watts/cm2, with energy fluence between 400 and 1,600 joules/cm2. Treatments were performed with local anesthesia on an outpatient basis. In all patients, marked improvements could be obtained after only a few treatments. Histologically there was necrosis of epidermis and dermis immediately after laser application, and ectatic vessels contained coagulated erythrocytes. Depth of coagulation was up to 3.5 mm. Quick restoration of epidermis was observed. After some days, macrophages, fibroblasts, and capillary blood vessels grew into the agglutination thrombi and ectatic vessels were replaced by granulation tissue and, later, by fibrous tissue. In comparison with the argon laser, the Nd-YAG laser coagulates at a much deeper level, but processes of tissue repair take longer and fibrosis is more pronounced after Nd-YAG laser application. Clinically, therefore, scar formation is more likely. Chilling the skin surface during irradiation and shorter exposure times may be effective in reducing the risk of scar formation in the future.

Neodymium-YAG laser therapy for vascular lesions.

The aim of the present study, which was performed at the dorsal aspects of the ears of guinea pigs, was to compare effects of different lasers on epidermis, dermis, and small venous vessels. Irradiations were performed with argon, dye, and Nd:YAG lasers. In the first series tissue repair processes were studied after argon laser application. Laser defects were excised after 1, 4, 8, and 14 days and were prepared for routine histological examination. The breadth of epidermal defect and extent of dermal coagulation and occlusion of vessels by thrombus formation were examined histologically. In a second series parameters of irradiation (ie, exposure time, laser power) of the three different lasers were changed systematically. Laser-induced morphological tissue changes could be best observed 24 hours after irradiation. Each of the lasers led to occlusion of vessels by thrombus formation and also coagulated epidermis and dermis. The extent of dermal and epidermal coagulation was less pronounced after dye laser application. Using short exposure times it was possible to reduce the extent of epidermal damage caused by argon and Nd:YAG lasers. Only 50-msec dye laser pulses led to intravascular thrombus formation without epidermal and dermal damage.

Effects of argon, dye, and Nd:YAG lasers on epidermis, dermis, and venous vessels.

In 18 patients, venous lakes, and in 77 patients, telangiectasias were successfully treated with the argon laser. Because treatments were easy to perform and patients were not impaired by therapy, the argon laser is the treatment of choice for these conditions in our experience.

Laser therapy of venous lakes (Bean-Walsh) and telangiectasias.

Fast 30 Jahre nachdem es dem Physiker Th. Maiman gelang, einen Laser zu bauen, werden diese in zahlreichen Disziplinen der Medizin erfolgreich eingesetzt (Tabelle 1). Die ersten dermatologischen Anwendungen gehen auf Professor L. Goldman zuruck, der bereits 1967 daruber berichtete [10]. Mittlerweile sind Laser ein fester Bestandteil der Dermatotherapie geworden, und es lassen sich absolute, relative und „kasuistische“ Indikationen fur die Lasertherapie abgrenzen. Uberwiegend werden dabei die thermisch-destruktiven Effekte der Laserstrahlen genutzt, d. h. krankhaftes Gewebe wird koaguliert, vaporisiert oder mit dem Lichtskalpell exzidiert.

Diether Dr Haina

Papers

Comparison of the maximum coagulation depth in human skin for different types of medical lasers.

Neodymium-YAG laser therapy for vascular lesions.

Effects of argon, dye, and Nd:YAG lasers on epidermis, dermis, and venous vessels.

Laser therapy of venous lakes (Bean-Walsh) and telangiectasias.

Lasertherapie in der Dermatologie