Proteomic Analysis of Mucosal and Systemic Responses to SARS-CoV-2 Antigen.

The mucosal environment of the upper respiratory tract is the first barrier of protection against SARS-CoV-2 transmission. However, the mucosal factors involved in viral transmission and potentially modulating the capacity to prevent such transmission have not fully been identified. In this pilot proteomics study, we compared mucosal and systemic compartments in a South African cohort of vaccinated and unvaccinated individuals undergoing maxillofacial surgery with previous history of COVID-19 or not. Inflammatory profiles were analyzed in plasma, nasopharyngeal swabs, and nasal and oral tissue explant cultures, using Olink and Luminex technologies. SARS-CoV-2-specific antibody levels were measured in serum and tissue explants. An increased pro-inflammatory proteomic profile was measured in the nasal compartment compared to plasma. However, IP-10 and MIG levels were higher in secretions than in nasal tissue, and the opposite was observed for TGF-ß. Nasal anti-SARS-CoV-2 spike IgG correlated with mucosal MIG expression for all participants. A further positive correlation was found with IP-10 in BioNTech/Pfizer-vaccinated individuals. Systemic levels of anti-SARS-CoV-2 spike IgG elicited by this vaccine correlated with plasma IL-10, IL-6 and HBD4. Proteomic profiles measured in mucosal tissues and secretions using combined technologies could reveal correlates of protection at the mucosal portals of viral entry.

SARS-CoV-2 variant spike and accessory gene mutations alter pathogenesis.

The ongoing COVID-19 pandemic is a major public health crisis. Despite the development and deployment of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pandemic persists. The continued spread of the virus is largely driven by the emergence of viral variants, which can evade the current vaccines through mutations in the spike protein. Although these differences in spike are important in terms of transmission and vaccine responses, these variants possess mutations in the other parts of their genome that may also affect pathogenesis. Of particular interest to us are the mutations present in the accessory genes, which have been shown to contribute to pathogenesis in the host through interference with innate immune signaling, among other effects on host machinery. To examine the effects of accessory protein mutations and other nonspike mutations on SARS-CoV-2 pathogenesis, we synthesized both viruses possessing deletions in the accessory genes as well as viruses where the WA-1 spike is replaced by each variant spike gene in a SARS-CoV-2/WA-1 infectious clone. We then characterized the in vitro and in vivo replication of these viruses and compared them to both WA-1 and the full variant viruses. Our work has revealed that the accessory proteins contribute to SARS-CoV-2 pathogenesis and the nonspike mutations in variants can contribute to replication of SARS-CoV-2 and pathogenesis in the host. This work suggests that while spike mutations may enhance receptor binding and entry into cells, mutations in accessory proteins may alter clinical disease presentation.

Post-COVID-19 Unusual Inflammatory Syndromes Detected on 18F-FDG PET/CT Scan.

ABSTRACT: SARS-CoV-2 is primarily known to cause respiratory symptoms. However, in this global COVID-19 pandemic, we have come across many extrapulmonary manifestations during and in the immediate post-COVID phase such as gastrointestinal symptoms, kidney and liver injury, myocardial dysfunction and acute coronary syndromes, and neurological, thromboembolic, dermatological, and musculoskeletal disorders. We present 2 such unusual cases of post-COVID complications-diffuse panniculitis and inflammatory myositis, as well as their clinical and FDG PET/CT imaging features.

Placental Pathology in COVID-19: Case Series in a Community Hospital Setting.

Objective To report the histopathologic findings in the placentas of pregnant women with coronavirus disease-19 (COVID-19). Methods Pregnant women with COVID-19 delivering between April 2020 to June 2020 were identified. A retrospective study of placentas from COVID positive women received in the Department of Pathology, Monmouth Medical Center affiliate of Robert Wood Johnson Barnabas Health were examined and compared to control cohort of placentas from COVID negative women. The mothers were tested for coronavirus through nasopharyngeal swab upon admission to labor and delivery. The placentas from mothers who tested negative for the virus were sent to Pathology for examination based on the obstetrician's clinical judgment. Results Fifty surgical specimens (49 placentas and one product of conception) from patients positive for COVID-19 were examined and compared with fifty placentas from women with negative COVID-19 test results, who delivered during the same period. Most of the neonates had Appearance, Pulse, Grimace, Activity and Respiration (APGAR) scores of 9 and 9 at 1 and 5 minutes, respectively. Increased incidence of the COVID-19 positivity was noted in individuals with Rh-positive blood group A and Jewish heritage. Compared to the control group, the COVID-19 positive placentas showed increased features of malperfusion (microcalcifications, fibrin thrombi, syncytial knotting, and villous agglutination). However, there was no significant dysregulation in other variables, such as inflammation or coagulation. There was no case of maternal or fetal death (greater than eight weeks) or evidence of worse fetal outcomes noted due to a mother's positive COVID-19 status.  Conclusions The COVID-19 positive placentas showed an increased prevalence of microcalcifications and fibrin thrombi, which may reflect an underlying hypercoagulable state induced by COVID-19 infection or could be due to excessive syncytiotrophoblast injury.