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BackgroundSeveral autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19.MethodsWe performed highly sensitive indirect immunofluorescence assays to detect anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed-up to one year after infection, eleven vaccinated individuals, and 41 unexposed controls.ResultsCompared to healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA- negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B cell compartment after recovery.ConclusionHighly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased anti-viral humoral immune responses and inflammatory immune signatures.

The frequency of extreme weather events, such as droughts, is assumed to increase and lead to alterations in ecosystem productivity and thus the terrestrial carbon cycle. Although grasslands typically show reduced productivity in response to drought, the effects of drought on grassland productivity have been shown to vary strongly. Here we tested, in a 2-year field experiment, if the resistance and the recovery of grasses to drought varies throughout a growing season and if the timing of the drought influences drought-induced reductions in annual aboveground net primary production (ANPP) of grasses. For the experiment we grew six temperate and perennial C3 grass species and cultivars in a field as pure stands. The grasses were cut six times during the growing season and subject to 10 week drought treatments that occurred either in the spring, the summer or the fall. Averaged across all grasses, drought-induced losses in productivity in spring were smaller (−20 % to −51 %) than in summer and fall (−77 % to −87 %). This suggests a higher resistance to drought in spring when plants are in their reproductive stage and their productivity is the highest. After the release from drought, we found no prolonged suppression in growth. In contrast, post-drought growth rates of formerly drought-stressed swards outperformed the growth rates of the control swards. The strong overcompensation in growth after the drought release resulted in relatively small overall drought-induced losses in annual ANPP that ranged from −4 % to −14 % and were not affected by the timing of the drought event. In summary, our results show that (i) the resistance in growth rates of grasses to drought varies across the season and is increased during the reproductive phenological stage when growth rates are highest; (ii) that the positive legacy effects of drought indicate a high recovery potential of temperate grasses to drought; and (iii) that the high recovery can compensate for immediate drought effects on total annual biomass production to a significant extent.

Background Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear. Objectives To evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases. Methods Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including SARS-CoV-2 polymerase chain reaction (PCR)+ patients (n = 64) as well as PCR+ and PCR– healthcare workers (n = 109). Results SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases were often transiently positive, whereas serum IgG titers remained negative or became positive 12–14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some healthcare workers with negative SARS-CoV-2-specific serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2-specific IgA titers in nasal fluids inversely correlated with age. Conclusions Systemic antibody production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA titers seen in patients with severe ARDS, whereas mild disease may be associated with transient production of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion., Graphical abstract, Our study suggests a model where the extent and duration of SARS-CoV-2-related clinical symptoms correlates with the systemic and mucosal virus-specific humoral immune responses, with implications for seroprevalence studies.

BackgroundInfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an acute illness termed coronavirus disease 2019 (COVID-19). Humoral immune responses likely play an important role in containing SARS-CoV-2, however, the determinants of SARS-CoV-2-specific antibody responses are unclear.MethodsUsing immunoassays specific for the SARS-CoV-2 spike protein, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including patients with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection (n = 56; median age 61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age 36 years) with or without symptoms and tested negative or positive by RT-qPCR.FindingsOn average, SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases became positive eight days after symptom onset and were often transient, whereas serum IgG levels remained negative or reached positive values 9–10 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers as a function of duration since symptom onset, independent of patient age and comorbidities. Very high levels of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum titers had detectable SARS-CoV-2-specific IgA antibodies in their nasal fluids and tears. Moreover, SARS-CoV-2-specific IgA levels in nasal fluids of these healthcare workers were inversely correlated with patient age.InterpretationThese data show that systemic IgA and IgG production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA levels seen in patients with severe ARDS, whereas mild disease may be associated with transient serum titers of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody responses dependent on COVID-19 severity.

The frequency of extreme weather events, such as droughts, is assumed to increase leading to alterations of ecosystem productivity and thus the terrestrial carbon cycle. Although grasslands typically show reduced productivity in response to drought, their effects have been shown to vary quite dramatically. Here we tested in a two-year field experiment, if the resistance and the resilience of grasses towards drought varies throughout a growing season and if the timing of drought, thus, influences drought-induced reductions in annual net primary production (NPP) of grasses. For the experiment we grew six temperate and perennial C3 grass species in a field as monocultures. The grasses were cut six times during the growing season and subject to 10-week drought treatments that occurred either in the spring, the summer or the fall. Across all species, drought-induced losses of productivity were smaller (−20 % to −51 %) than in summer and fall (−77 % to −87 %). This suggests a higher resistance to drought in spring when the productivity of the grasses is the highest and plants are in their reproductive stage. After the release of drought, we found no prolonged suppression of growth. In contrast, post-drought growth rates of formerly drought-stressed swards outperformed the growth rates of the control swards. In 2014, the overcompensation after drought release was similar in all seasons, but differed in 2015. The strong overcompensation of growth after drought release resulted in relatively small overall drought-induced losses of annual ANPP that ranged between −4 % to −14 % and were not affected by the timing of the drought event. Our results show that (i) the resistance of growth rates in grasses to drought varies across the season and is positively correlated with growth rates in the control, (ii) that positive legacy effects of drought indicate a high resilience of temperate grasses to drought, and (iii) that the high resilience can compensate immediate drought effects on total annual biomass production to a large extent.