The coronavirus disease (COVID-19) imposes an unusual risk to the physical and mental health of healthcare workers and thereby to the functioning of healthcare systems during the crisis. This study investigates the clinical knowledge of healthcare workers about COVID-19, their ways of acquiring information, their emotional distress and risk perception, their adherence to preventive guidelines, their changed work situation due to the pandemic, and their perception of how the healthcare system has coped with the pandemic. It is based on a quantitative cross-sectional survey of 185 Swiss healthcare workers directly attending to patients during the pandemic, with 22% (n = 40) of them being assigned to COVID-19-infected patients. The participants answered between 16th June and 15th July 2020, shortly after the first wave of COVID-19 had been overcome and the national government had relaxed its preventive regulations to a great extent. The questionnaire incorporated parts of the “Standard questionnaire on risk perception of an infectious disease outbreak” (version 2015), which were adapted to the case of COVID-19. Clinical knowledge was lowest regarding the effectiveness of standard hygiene (p < 0.05). Knowledge of infectiousness, incubation time, and life-threatening disease progression was higher, however still significantly lower than regarding asymptomatic cases and transmission without physical contact (p < 0.001). 70% (95%-confidence interval: 64-77%) of the healthcare workers reported considerable emotional distress on at least one of the measured dimensions. They worried significantly more strongly about patients, elderly people, and family members, than about their own health (p < 0.001). Adherence to (not legally binding) preventive guidelines by the government displayed patterns such that not all guidelines were followed equally. Most of the participants were faced with a lack of protective materials, personnel, structures, processes, and contingency plans. An increase in stress level was the most prevalent among the diverse effects the pandemic had on their work situation. Better medical equipment (including drugs), better protection for their own mental and physical health, more (assigned) personnel, more comprehensive information about the symptoms of the disease, and a system of earlier warning were the primary lessons to be learned in view of upcoming waves of the pandemic.