Human WM9 melanoma cells, previously shown to be devoid of PDGF expression, were stably transfected with a PDGF-B cDNA under the transcriptional control ofa cytomegalovirus promoter. Northern blot analysis revealed

ObjectivesUncontrolled thromboinflammation plays an important role in the pathogenesis of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus. Complement was implicated as key contributor to this process, therefore we hypothesized that markers of the complement profile, indicative for the activation state of the system, may be related to the severity and mortality of COVID-19.MethodsIn this prospective cohort study samples of 102 hospitalized and 26 outpatients with PCR-confirmed COVID-19 were analyzed. Primary outcome was in-hospital, COVID-19 related mortality, and secondary outcome was COVID-19 severity as assessed by the WHO ordinal scale. Complement activity of alternative and classical pathways, its factors, regulators, and activation products were measured by hemolytic titration, turbidimetry, or enzyme-immunoassays. Clinical covariates and markers of inflammation were extracted from hospital records.ResultsIncreased complement activation was characteristic for hospitalized COVID-19 patients. Complement activation was significantly associated with markers of inflammation, such as interleukin-6, C-reactive protein, and ferritin. Twenty-five patients died during hospital stay due to COVID-19 related illness. Patients with uncontrolled complement activation leading to consumption of C3 and decrease of complement activity were more likely to die, than those who had complement activation without consumption. Cox models identified anaphylatoxin C3a, and C3 overactivation and consumption (ratio of C3a/C3) as predictors of in-hospital mortality [HR of 3.63 (1.55–8.45, 95% CI) and 6.1 (2.1–17.8), respectively].ConclusionIncreased complement activation is associated with advanced disease severity of COVID-19. Patients with SARS-CoV-2 infection are more likely to die when the disease is accompanied by overactivation and consumption of C3. These results may provide observational evidence and further support to studies on complement inhibitory drugs for the treatment of COVID-19.

In the present study, humoral and T cell-mediated immune responses elicited by BBIBP-CorV (inactivated virus) and BNT162b2 (mRNA-based) vaccines against SARS-CoV-2 virus were compared. Convalescent volunteers were also investigated to evaluate adaptive immunity induced by live virus. Although both vaccines induced antibody- and T cell-mediated immune responses, our analysis revealed significant quantitative and qualitative differences between the two types of challenges. The BBIBP-CorV vaccine elicited antireceptor-binding domain (RBD) IgG, as well as anti-spike protein (S) IgG and IgA antibodies in healthy individuals, the levels of which were much lower than after BNT162b2 vaccination but still higher than in the convalescent patients. The cumulative IFNγ-positive T cell response, however, was only twofold higher in participants injected with BNT162b2 compared to those who were primed and boosted with BBIBP-CorV vaccine. Moreover, the inactivated virus vaccine induced T cell response that targets not only the S but also the nucleocapsid (N) and membrane (M) proteins, whereas the mRNA vaccine was able to elicit a much narrower response that targets the S protein epitopes only. Thus, the pattern of BBIBP-CorV-induced T cell response in virus-naive participants was similar to the cell-mediated anti-SARS-CoV-2 response observed in convalescent patients. Based on these data, we can conclude that the BBIBP-CorV inactivated virus vaccine is immunologically effective. However, the duration of BBIBP-CorV-induced integrated, antibody, and T cell-mediated, immune responses needs further investigation.

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From March through December 2020, 100 autopsies were performed (Semmelweis University, Budapest, Hungary), with chart review, of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection demonstrated by real-time reverse-transcription polymerase chain reaction testing (mean age, 74.73 years, range 40–102 years; 50 males, mean age 71.96 years, and 50 females, mean age 77.5 years). Classified by the date of death, 21 cases were from the pandemic’s “first wave” (March through July) and 79 from the “second wave” (August through December). Three mortality categories were defined by relevance of SARS-CoV-2 infection: (1) “strong” association (n=57), in which COVID-19 was primary responsible for death; (2) “contributive” association (n=27), in which a pre-existing condition independent of COVID-19 was primary responsible for death, albeit with substantial COVID-19 co-morbidity; (3) “weak” association (n=16), in which COVID-19 was minimally or not at all responsible for death. Distributions among categories differed between the first wave, in which the “contributive” association cases dominated (strong: 24%, contributive: 48%, weak: 28%), and the second wave, in which the “strong” association cases dominated (strong: 66%, contributive: 21%, weak: 13%). Charted co-morbidities included hypertension (85 %), cardiovascular diseases (71 %), diabetes (40 %), cerebrovascular diseases (31 %), chronic respiratory diseases (30 %), malignant tumors (20 %), renal diseases (19 %), diseases of the central nervous system (15 %), and liver diseases (6 %). Autopsy evaluation analyzed alterations on macroscopy as well as findings on microscopy of scanned and scored sections of formalin-fixed, paraffin-embedded tissue samples (50–80 blocks/case). Severity of histological abnormalities in the lung differed significantly between “strong” and “contributive” (p<0.0001) and between “strong” and “weak” categories (p<0.0001). Abnormalities included diffuse alveolar damage, macrophage infiltration, and vascular and alveolar fibrin aggregates (lung), with macro- and microvascular thrombi and thromboemboli (lung, kidney, liver). In conclusion, autopsies clarified in what extent COVID-19 was responsible for death, demonstrated the pathological background of clinical signs and symptoms, and identified organ alterations that led to the death. Clinicopathologic correlation, with conference discussions of severity of co-morbidities and of direct pathological signs of disease, permitted accurate categorization of cause of death and COVID-19 association as “strong,” “contributive,” or “weak.” Lung involvement, with reduced ventilatory capacity, was the primary cause of death in the “strong” and “contributive” categories. Shifts in distribution among categories, with “strong” association between COVID-19 and death dominating in the second wave, may reflect improved clinical management of COVID-19 as expertise grew.