Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation.

Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein-Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p < 0.001, Fisher's exact test). A similar ratio was observed in a secondary group of 18 subjects 21-90 days after testing positive for COVID-19, indicating reactivation may occur soon after or concurrently with COVID-19 infection. These findings suggest that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of COVID-19 inflammation-induced EBV reactivation.

Comparison of the immune response following subcutaneous versus intranasal modified-live virus booster vaccination against bovine respiratory disease in pre-weaning beef calves that had received primary vaccination by the intranasal route.

This study was performed to elucidate whether the route of booster vaccination affects the immune response against respiratory vaccine viruses in pre-weaning beef calves that receive primary intranasal (IN) vaccination during the first month of life. The objective was to compare the serum neutralizing antibody (SNA) titers to BHV1, BRSV, and BPI3V, cytokine mRNA expression and mucosal BHV1- and BRSV-specific IgA in nasal secretions following administration of IN or subcutaneous (SC) modified-live virus (MLV) booster vaccines 60 days after primary IN vaccination in young beef calves. Twenty-one beef calves were administered 2 mL of an IN MLV vaccine containing BHV1, BRSV, and BPI3V (Inforce3®) between one and five weeks of age. Sixty days after primary vaccination, calves were randomly assigned to one of two groups: IN-MLV (n = 11): Calves received 2 mL of the same IN MLV vaccine used for primary vaccination and 2 mL of a SC MLV vaccine containing BVDV1 & 2 (Bovi- Shield GOLD® BVD). SC-MLV (n = 10): Calves were administered 2 mL of a MLV vaccine containing, BHV1, BRSV, BPI3V, and BVDV1 & 2 (Bovi-Shield GOLD® 5). Blood and nasal secretion samples were collected on days -61 (primary vaccination), -28, -14, 0 (booster vaccination), 14, 21, 28, 42 and 60 for determination of SNA titers, cytokine gene expression analysis and nasal virus-specific IgA concentrations. Statistical analysis was performed using a repeated measures analysis through PROC GLIMMIX of SAS®. Booster vaccination by neither IN nor SC routes induced a significant increase in SNA titers against BHV1, BRSV, and BPI3V. Subcutaneous booster vaccination induced significantly greater BRSV-specific SNA titers (on day 42) and IgA concentration in nasal secretions (on days 21 and 42) compared to calves receiving IN booster vaccination. Both IN and SC booster vaccination were able to stimulate the production of BHV1-specific IgA in nasal secretions. In summary, booster vaccination of young beef calves using either SC or IN route two months after IN MLV primary vaccination resulted in comparable SNA titers, cytokine gene expression profile and virus-specific IgA concentration in nasal secretions. Only a few differences in the systemic and mucosal immune response against BHV1 and BRSV were observed. Subcutaneous booster vaccination induced significantly greater BRSV-specific SNA and secretory IgA titers compared to IN booster vaccination.

Analysis of Measles-Mumps-Rubella (MMR) Titers of Recovered COVID-19 Patients.

The measles-mumps-rubella (MMR) vaccine has been theorized to provide protection against coronavirus disease 2019 (COVID-19). Our aim was to determine whether any MMR IgG titers are inversely correlated with severity in recovered COVID-19 patients previously vaccinated with MMR II. We divided 80 subjects into two groups, comparing MMR titers to recent COVID-19 severity levels. The MMR II group consisted of 50 subjects who would primarily have MMR antibodies from the MMR II vaccine, and a comparison group of 30 subjects consisted of those who would primarily have MMR antibodies from sources other than MMR II, including prior measles, mumps, and/or rubella illnesses. There was a significant inverse correlation (rs = -0.71, P < 0.001) between mumps virus titers (mumps titers) and COVID-19 severity within the MMR II group. There were no significant correlations between mumps titers and severity in the comparison group, between mumps titers and age in the MMR II group, or between severity and measles or rubella titers in either group. Within the MMR II group, mumps titers of 134 to 300 arbitrary units (AU)/ml (n = 8) were found only in those who were functionally immune or asymptomatic; all with mild symptoms had mumps titers below 134 AU/ml (n = 17); all with moderate symptoms had mumps titers below 75 AU/ml (n = 11); all who had been hospitalized and had required oxygen had mumps titers below 32 AU/ml (n = 5). Our results demonstrate that there is a significant inverse correlation between mumps titers from MMR II and COVID-19 severity.IMPORTANCE COVID-19 has presented various paradoxes that, if understood better, may provide clues to controlling the pandemic, even before a COVID-19 vaccine is widely available. First, young children are largely spared from severe disease. Second, numerous countries have COVID-19 death rates that are as low as 1% of the death rates of other countries. Third, many people, despite prolonged close contact with someone who is COVID-19 positive, never test positive themselves. Fourth, nearly half of people who test positive for COVID-19 are asymptomatic. Some researchers have theorized that the measles-mumps-rubella (MMR) vaccine may be responsible for these disparities. The significance of our study is that it showed that mumps titers related to the MMR II vaccine are significantly and inversely correlated with the severity of COVID-19-related symptoms, supporting the theorized association between the MMR vaccine and COVID-19 severity.