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The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Some physical phenomena associated with the anxiety states and their relation to hyperventilation
(1937)
The authors believe that there is a physiological background for the perseverance of an anxiety state as part of a psychoneurosis; that this background is produced by the constant presence of purely emotional disturbances; and that the resultant physiological state aggravates the psychic component to such a degree that a vicioris cycle is instituted, the symptoms of which are manifold. These symptoms increase the severity of the emotional tension ; and, if they are prolonged, permanent structural change with the production of organic clisease results. The mechanism is at first a repetition of attacks, from the stimulation by an emotion such as fear upon the sympathetic nervous system, which in turn becomes increasingly labile. The mechanism is perpetuated by the effects of the simulus on the system of self-defense, which is dispatched by the endocrine group. This reaction causes a state of hyperirritability to exist through the presence of tissue alkalosis, tissue liydremia, and tissue anoxemia; and results in a state of tetany which may be regional or generalized. The Symptoms of tetany, and allied rnanifestations such ac tachycardia, distended stomach and dilated urinary bladder, are enough to aggravate the neurosis because of the patient's fear of impending dissolution. Multiplication of impulses increases the bombardment of the sympathetic nervous system, making repetition of tlie reaction more easy at subsequent intervals. The cure is accomplished through elimination of tlie fear-impulse by psychotherapy. The symptoms may be alleviated medically, and by this rneans that part of the neurosis which is on the basis of anxiety concerning health may be eliminated. Because of the subjective and objective improvement in the patient's condition, contact for psychotherapy is more easily obtained. Medical treatment is directed toward preservation of the acid-base balance; toward decreasing the effect of adrenalin on the nerve-tissue by means of a known chemical antagonist; or toward converting the state of tone of the individual from extreme to moderate, whether parasympathic or sympathetic in type.