*p< 0.05; **p< 0.01; Tukey-Kramer test. For granulocytes we gated SSChicells and then differentiated subpopulations by their expression patterns for CD11b, CD16 and CD177. of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1+cytotoxic YHO-13177 T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched, whereas all other parameters returned to baseline. Our findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcomes. Keywords:SARS-CoV-2, COVID-19, disease phases, plasmablasts, cytotoxic T cells, IP-10, YHO-13177 acute contamination, antibodies == 1. Introduction == The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is usually a highly infectious and rapidly transmittable -coronavirus that led to the global pandemic of coronavirus disease 2019 (COVID-19). As of summer 2021, more than 180 million people were infected, with almost 4 million casualties worldwide [1,2]. Of great concern are new virus variants that emerge periodically and exhibit augmented pandemic potentials, can cause contamination of individuals vaccinated against the original strain, and re-infect patients previously recovered from COVID-19 [3,4]. COVID-19 is usually characterized by a diverse collection of isolated or combined symptoms ranging from moderate to severe to life-threatening. While moderate disease may proceed asymptomatic or show mere signs of a common cold, moderate and severe COVID-19 present with symptoms that range from fever, malaise and fatigue to neurological, dermatological, gastrointestinal and pulmonary manifestations [5]. Pneumonia may lead to an acute respiratory distress syndrome (ARDS), necessitating oxygen supplementation and mechanical ventilation [6,7]. Immense effort has been put into the pathophysiological and immunological profiling of the host reaction to the disease [8,9]. Thus, a dysregulated host immune response was identified that causes a life-threatening cytokine storm and subsequent immune paralysis, leading to multiple organ failure and death. And even though mild-to-moderate COVID-19 does not seem to be associated GDF2 with a fulminant immune activation, more and more data point to long lasting contamination related sequelae including persisting nausea, fatigue and loss of smell and taste in up to 30% of patients who recovered from COVID-19 [10,11,12]. Hence, even non-severe COVID-19 may pose a considerable hazard for global health and the international economy. Although numerous studies have already addressed the differences between pathological profiles of severe and mild-to-moderate COVID-19, longitudinal trajectories within the circulating immune landscapes are still obscure [13,14]. However, a rapid identification of distinct disease stages might in the future allow for refined strategies with immunomodulatory therapies that support the hosts immune response. These therapies may indeed gain importance as more and more variants may emerge thatdespite efficient vaccination strategiesrequire the containment of viral loads after infection. In order to rule out any bias from immunosuppressive therapy in severe COVID-19, we chose to concentrate on mild-to-moderate cases and to analyze the peripheral blood immune cell composition and its activation, plasma levels of cytokines, and SARS-CoV-2 specific immunoglobulins. We then examined the YHO-13177 complementary data sets for transient alterations in consecutive samples, indicative for differently progressed disease. Finally, we suggested distinct YHO-13177 disease phases and characterized their immunological and serological layout. == 2. Materials and Methods == == 2.1. Study Population == COVID-19 patients were recruited either from the local COVID-19 test center or from the division of tropical medicine and infectious diseases. After an initial withdrawal of peripheral blood on the day of testing or admittance to the hospital (day one), subsequent venipunctures followed on days three and seven. Individuals recruited at the test center who were tested negative were considered healthy controls and they were required to provide blood only once on the day of testing. Apart.