Background Post-vaccination myopericarditis is reported after immunization with COVID-19 mRNA-vaccines. The effect of accidental intravenous injection of this vaccine on the heart is unknown. Methods We compared the clinical manifestations, histopathological changes, tissue mRNA expression and serum levels of cytokine/chemokine in Balb/c mice at different time points after intravenous(IV) or intramuscular(IM) vaccine injection with normal saline(NS) control. Results Though significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1 to 2 days post-injection(dpi), only IV group developed histopathological changes of myopericarditis as evidenced by cardiomyocyte degeneration, apoptosis and necrosis with adjacent inflammatory cell infiltration and calcific deposits on visceral pericardium, while evidence of coronary artery or other cardiac pathologies was absent. SARS-CoV-2 spike antigen expression by immunostaining was occasionally found in infiltrating immune cells of the heart or injection site, in cardiomyocytes and intracardiac vascular endothelial cells, but not skeletal myocytes. The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose. Cardiac tissue mRNA expression of IL-1β, IFN-β, IL-6 and TNF-α increased significantly from 1dpi to 2dpi in IV but not IM group, compatible with presence of myopericarditis in IV group. Ballooning degeneration of hepatocytes was consistently found in IV group. All other organs appeared normal. Conclusions This study provided in-vivo evidence that inadvertent intravenous injection of COVID-19 mRNA-vaccines may induce myopericarditis. Brief withdrawal of syringe plunger to exclude blood aspiration may be one possible way to reduce such risk.

Older individuals are at higher risk of SARS-CoV-2 infection and severe outcomes, but the underlying mechanisms are incompletely understood. In addition, how age modulates SARS-CoV-2 re-infection and vaccine breakthrough infections remain largely unexplored. Here, we investigated age-associated SARS-CoV-2 pathogenesis, immune responses, and the occurrence of re-infection and vaccine breakthrough infection utilizing a wild-type C57BL/6N mouse model. We demonstrated that interferon and adaptive antibody response upon SARS-CoV-2 challenge are significantly impaired in aged mice compared to young mice, which results in more effective virus replications and severe disease manifestations in the respiratory tract. Aged mice also showed increased susceptibility to re-infection due to insufficient immune protection acquired during the primary infection. Importantly, two-dose COVID-19 mRNA vaccination conferred limited adaptive immune response among the aged mice, making them susceptible to SARS-CoV-2 infection. Collectively, our findings call for tailored and optimized treatments and prevention strategies against SARS-CoV-2 among older individuals.

Background The role of SARS-CoV-2 in the pathogenesis of testicular damage is uncertain. Methods We investigated the virological, pathological, and immunological changes in testes of hamsters challenged by SARS-CoV-2 wild-type and its variants by intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control. Results Besides self-limiting respiratory tract infection, intranasal SARS-CoV-2 challenge caused acute decrease in sperm count, and serum testosterone and inhibin B at 4 to 7 days post-infection (dpi), and subsequently reduced testicular size and weight, and serum sex hormone level at 42 to 120 dpi. Acute histopathological damage with varying degree of testicular inflammation, haemorrhage, and necrosis, degeneration of seminiferous tubules and disruption of orderly spermatogenesis were seen with increasing virus inoculum. Degeneration and necrosis of Sertoli and Leydig cells were found. Though viral loads and SARS-CoV-2 nucleocapid (N) protein expression were markedly lower in testicular than lung tissues, direct intra-testicular injection showed N expressing interstitial cells and epididymal epithelial cells. Control intranasal or intra-testicular challenge by A(H1N1)pdm09 showed no testicular infection or damage. From 7 to 120 dpi, degeneration and apoptosis of seminiferous tubules, immune complex deposition and depletion of spermatogenic cell and spermatozoa persisted. Intranasal challenge with Omicron and Delta variants could also induce similar testicular changes. These testicular damages can be prevented by vaccination. Conclusions SARS-CoV-2 can cause acute testicular damage with subsequent chronic asymmetric testicular atrophy and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent COVID-19 males.

Background Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the Coronavirus Disease 2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described. Methods Two-dose (14 days apart) vaccination regimen with a formalin-inactivated whole virion SARS-CoV-2 in golden Syrian hamster model was established. To investigate the disease phenotypes of a one-dose regimen given 3 days prior (D-3), 1 (D1) or 2 (D2) days after, or on the day (D0) of virus challenge, we monitored the serial clinical severity, tissue histopathology, virus burden, and antibody response of the vaccinated hamsters. Results The one-dose vaccinated hamsters had significantly lower clinical disease severity score, body weight loss, lung histology score, nucleocapsid protein expression in lung, infectious virus titres in the lung and nasal turbinate, inflammatory changes in intestines and a higher serum neutralizing antibody or IgG titre against the spike receptor-binding domain or nucleocapsid protein when compared to unvaccinated controls. These improvements were particularly noticeable in D-3, but also in D0, D1 and even D2 vaccinated hamsters to varying degrees. No increased eosinophilic infiltration was found in the nasal turbinate, lung, and intestine after virus challenge. Significantly higher serum titre of fluorescent foci microneutralization inhibition antibody was detected in D1 and D2 vaccinated hamsters at day 4 post-challenge compared to controls despite undetectable neutralizing antibody titre. Conclusions Vaccination just before or soon after exposure to SARS-CoV-2 does not worsen disease phenotypes and may even ameliorate infection.

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