Highlights d Phosphoproteomics analysis of SARS-CoV-2-infected cells uncovers signaling rewiring d Infection promotes host p38 MAPK cascade activity and shutdown of mitotic kinases d Infection stimulates CK2-containing filopodial protrusions with budding virus d Kinase activity analysis identifies potent antiviral drugs and compounds

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The effects of combined intranasal and systemic glucocorticoid steroids on the local inflammatory response, and symptoms due to experimental rhinovirus infection were studied in 45 adults randomized to prophylaxis with either placebo or steroids. Intranasal beclomethasone (168 micrograms twice a day) was begun 4 days before viral challenge and continued 5 days after challenge. Oral prednisone (30 mg twice daily) was given for 3 days beginning 1 day before challenge. During the first 48 h after viral inoculation, nasal obstruction, nasal mucus weights, and kinin concentrations in nasal lavages were lower in steroid recipients, but subsequent increases in these variables in the steroid group resulted in no significant cumulative differences between treatment groups. These data suggest that steroid prophylaxis may suppress nasal inflammation and cold symptoms during the first 2 days in experimental rhinovirus colds.

This paper describes the longitudinal changes in nasal patency, mucociliary clearance rate, eustachian tube function, and middle ear pressure in a group of 40 volunteers infected with rhinovirus type 39. Thirty-two (80%) of the volunteers werejudged to have had a cold based on the modified Jackson criteria. Common symptoms included malaise, nasal congestion, rhinorrhea, and sneezing that began on the day after challenge and peaked in intensity on days 3-5. Nasal patency evaluated by active posterior rhinomanometry and mucociliary clearance rate evaluated by the dyed sacharrin technique were significantly decreased following challenge. For nasal patency the effect was primarily limited to days 2-8 postchallenge, while abnormalities in clearance rate were documented for as long as 18 days postchallenge. A 50% increased incidence of abnormal eustachian tube function and a 30% increased incidence of abnormal middle ear pressures were observed for days 2-7 postchallenge with a gradual return to baseline by day 16. For mucociliary clearance, eustachian tube function, and middle ear pressure, but not nasal patency, these abnormalities were more pronounced in patients with a symptomatic cold. These results show that changes in nasal physiology resulting from a rhinovirus infection can be objectively quantified and that the resulting pathophysiology extends to anatomically contiguous structures such as the eustachian tube and middle ear.