Improved Immunogenicity of the Inactivated F Genotype Mumps Vaccine against Diverse Circulating Mumps Viruses in Mice.

Mumps is an acute infectious disease caused by the mumps virus (MuV). Despite high global vaccination coverage, mumps outbreaks continue to occur, even in vaccinated populations. Therefore, we aimed to identify candidate vaccines that can induce an immunogenic response against diverse MuV genotypes with greater efficacy than the currently available options. Vaccine candidates were sourced using formalin-inactivated viral strains. The inactivated vaccines were administered to BALB/c mice (through a primer and booster dose administered after a three-week interval). We tested the neutralizing antibodies of the candidate vaccines against various MuV genotypes to determine their overall efficacy. The formalin-inactivated F genotype vaccine was found to have higher cross-neutralizing titers against genotypes F, H, and G as well as significant Th1 cytokines responses, IFN-γ, TNF-α, and IL-2 than the Jeryl Lynn (JL) vaccine. Our findings suggest that the inactivated F genotype mumps vaccine has higher immunogenicity than the JL vaccine against diverse circulating MuVs.

A highly efficacious live attenuated mumps virus-based SARS-CoV-2 vaccine candidate expressing a six-proline stabilized prefusion spike.

With the rapid increase in SARS-CoV-2 cases in children, a safe and effective vaccine for this population is urgently needed. The MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines used in infants and children since the 1960s. Here, we developed live attenuated recombinant mumps virus (rMuV)-based SARS-CoV-2 vaccine candidates using the MuV Jeryl Lynn (JL2) vaccine strain backbone. The soluble prefusion SARS-CoV-2 spike protein (preS) gene, stablized by two prolines (preS-2P) or six prolines (preS-6P), was inserted into the MuV genome at the P-M or F-SH gene junctions in the MuV genome. preS-6P was more efficiently expressed than preS-2P, and preS-6P expression from the P-M gene junction was more efficient than from the F-SH gene junction. In mice, the rMuV-preS-6P vaccine was more immunogenic than the rMuV-preS-2P vaccine, eliciting stronger neutralizing antibodies and mucosal immunity. Sera raised in response to the rMuV-preS-6P vaccine neutralized SARS-CoV-2 variants of concern, including the Delta variant equivalently. Intranasal and/or subcutaneous immunization of IFNAR1-/- mice and golden Syrian hamsters with the rMuV-preS-6P vaccine induced high levels of neutralizing antibodies, mucosal immunoglobulin A antibody, and T cell immune responses, and were completely protected from challenge by both SARS-CoV-2 USA-WA1/2020 and Delta variants. Therefore, rMuV-preS-6P is a highly promising COVID-19 vaccine candidate, warranting further development as a tetravalent MMR vaccine, which may include protection against SARS-CoV-2.

Case of COVID-19 Related Thyroiditis

Introduction: The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a novel enveloped RNA beta-coronavirus responsible for the Coronavirus disease-19 (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. The SARS-CoV-2 pandemic has spread rapidly worldwide. Few cases and case series have been published reporting COVID-19 related subacute thyroiditis. We report a case of COVID-19 related thyroiditis. Case Description: 73-year-old female presented to the hospital with complaint of shortness of breath, fever and weakness. She was diagnosed with COVID-19 pneumonia and treated with dexamethasone and convalescent plasma. Patient was discharged home after 10 days. Two days after discharge, she presented with complaint of generalized weakness. She was noted to have thyrotoxicosis. Patient was not taking lithium or amiodarone and she did not receive iodinated contrast. She had no sign or symptoms of thyrotoxicosis. She denied neck pain or difficulty swallowing. On laboratory evaluation, SARS Coronavirus 2 RNA was positive. RSV, Influenza A and Influenza B by PCR were negative. TSH was low at 0.182 uIU/mL (0.450-5.330 uIU/mL), free T4 elevated at 3.00 ng/dL (0.58-1.64 ng/dL), free T3 elevated at 5.24 pg/mL (2.20-4.10 pg/mL). Her TSH 3 weeks ago was normal at 0.723 uIU/mL. Thyroid stimulating immunoglobulin negative < 0.10 (< =0.54 IU/L). Thyroid ultrasound showed normal sized gland, few sub centimeter nodules bilaterally. NM thyroid uptake and scan showed low uptake and no focal hot or cold nodule. Her workup was consistent with thyroiditis. Correlating with the diagnosis of COVID-19, this could be most likely COVID-19 related thyroiditis. Repeat labs in a week showed normal TSH 1.138 uIU/mL, normal free T4 1.28 ng/dL and low free T3 1.93 pg/mL. The patient likely had thyroiditis during early course of COVID-19 infection and was caught during the late phase and hence, improvement of thyroid function within a week of biochemical diagnosis. Discussion: Subacute thyroiditis is a self-limited inflammatory disorder, characterized by neck pain, general symptoms and thyroid dysfunction. It has been linked to viral infection like mumps virus, coxsackievirus, adenovirus, Epstein-Barr virus, rubella and cytomegalovirus. In our patient, SARS-CoV-2 was the likely cause of thyroiditis. A single center retrospective study done in 287 patients hospitalized with COVID-19 in Milan, Italy reported 20% of patients with thyrotoxicosis, 5% with hypothyroidism and 74% with normal thyroid function test. We report this case to alert clinicians that thyroiditis and resultant thyrotoxicosis should always be considered as a differential diagnosis in patients with COVID-19.

Vitamin A and viral infection in critical care

Vitamin A is fat-soluble compounds of retinoid derivate, consisting of retinol, retinal, and retinyl esters. Vitamin A also affects cell growth and differentiation, playing a critical role in the normal formation and function of the heart, lungs, kidneys, and other organs. According to the role of vitamin A in enhancing immune function, it is known as an anti-inflammatory agent. Also, vitamin A supplementation by reducing morbidity and mortality in different infectious diseases, such as measles, diarrheal disease, measles-related pneumonia, human immunodeficiency virus infection, and malaria considered as a crucial factor against infection. So vitamin A deficiency can be life-threatening, because of impairing the response to infection and significant risk of development of severe respiratory infections in infants and young children. In this paper, we have discussed the effects of vitamin A in modulating immune responses in viral infections and the direct effects of this vitamin on viral replication by comparing its role during different types of viral infections.

Summary of national data of class A, B and C communicable diseases in China, October 2021

In October 2021 (from 00: 00, 1 October to 24: 00, 31 October), a total of 523 006 cases of notifiable communicable diseases, including 2 040 deaths, were reported in China (except Hong Kong, Macao Special Administrative Regions and Taiwan Province, the same below). In communicable diseases in class A, 2 cases of cholera were reported without death. In communicable diseases in class B, no cases and no deaths of severe acute respiratory syndrome, poliomyelitis, human infection with highly pathogenic avian influenza virus, diphtheria and human infection with avian influenza A (H7N9) virus were reported. For the remaining 22 communicable diseases in class B, 249 605 cases were reported, a decrease of 8% compared with last month (272 332 cases) and a decrease of 3% compared with the same period in 2020 (258 591 cases). The first 5 diseases in terms of reported case number were viral hepatitis, pulmonary tuberculosis, syphilis, gonorrhea and AIDS, accounting for 95% of the total reported cases in class B. A total of 2 039 deaths were reported, a decrease of 6% (133 deaths) compared with last month (2 172 deaths) and an increase of 17% compared with the same period in 2020 (1 737 deaths). According to the website of the National Health Commission of China, a total of 1 081 confirmed COVID-19 cases were reported, without death, by 31 provinces (municipalities, autonomous regions) and Xinjiang Production and Construction Corps from 00: 00, 1 October to 24: 00, 31 October, 2021. In class C communicable diseases, a total of 273 399 cases were reported, an increase of 20% compared with last month (228 597 cases) and a decrease of 13% compared with the same period in 2020 (315 366 cases). The first 3 diseases in terms of reported case number were hand foot and mouth disease (HFMD), other infectious diarrhea and influenza, accounting for 95% of the total reported cases in class C. Compared with last month, except filariasis which had no incidences in both months, the diseases with reported cases increases were HFMD (45 435 cases, 52%), influenza (17 811 cases, 50%) and rubella (11 cases, 12%), but the reported cases of other diseases all decreased, the diseases with obvious case decreases were other infectious diarrhea (16 519 cases, 18%), mumps (1 490 cases, 12%) and acute hemorrhagic conjunctivitis (327 cases, 14%). Compared with the same period in 2020, except filariasis which had no incidences in both years, the diseases with reported case increases were influenza (33 177 cases, 164%), typhus fever (15 cases, 9%), rubella (8 cases, 9%) and leprosy (3 cases, 17%), but the diseases with reported case decreases were HFMD (65 002 cases, 33%), other infectious diarrhea (4 111 cases, 5%) and mumps (1 574 cases, 12%). One death caused by class C communicable diseases was reported, an increase of 1 death compared with last month and a decrease of 1 death compared with the same period in 2020 (2 deaths).

Summary of national data of class A, B and C communicable diseases in China, September 2021

In September 2021 (from 00:00, 1 September to 24: 00, 30 September), a total of 500 929 cases of notifiable communicable diseases, including 2 172 deaths, were reported in China (except Hong Kong, Macao Special Administrative Regions and Taiwan Province, the same below). In communicable diseases in class A, no case and no death were reported. In communicable diseases in class B, no cases and no deaths of severe acute respiratory syndrome, poliomyelitis, human infection with highly pathogenic avian influenza virus, diphtheria and human infection with avian influenza A(H7N9) virus were reported. For the remaining 22 communicable diseases in class B, 272 332 cases were reported, a decrease of 0.9% compared with last month (274 917 cases) and a decrease of 5% compared with the same period in 2020 (287 923 cases). The first 5 diseases in terms of reported case number were viral hepatitis, pulmonary tuberculosis, syphilis, gonorrhea and brucellosis, accounting for 94% of the total reported cases in class B. A total of 2 172 deaths were reported, an increase of 5% (95 deaths) compared with last month (2 077 deaths) and a decrease of 5% compared with the same period in 2020 (2 291 deaths). According to the website of the National Health Commission of China, a total of 1 264 confirmed COVID-19 cases were reported, without death, by 31 provinces (municipalities, autonomous regions) and Xinjiang Production and Construction Corps from 00:00, 1 September to 24: 00, 30 September, 2021. In class C communicable diseases, a total of 228 597 cases were reported, an increase of 10% compared with last month (207 153 cases) and a decrease of 7% compared with the same period in 2020 (247 112 cases). The first 3 diseases in terms of reported case number were other infectious diarrhea, hand foot and mouth disease (HFMD) and influenza, accounting for 93% of the total reported cases in class C. Compared with last month, except filariasis, visceral leishmaniasis, leprosy and other infectious diarrhea which decreased by 1 case, 11 cases (39%), 12 cases (33%) and 12 747 cases (12%) respectively, the reported cases of all other diseases increased, the diseases with obvious case increases were HFMD (15 352 cases, 22%), influenza (14 160 cases, 66%) and mumps (4 253 cases, 51%). Compared with the same period in 2020, the diseases with reported case increases were influenza (17 269 cases, 95%), visceral leishmaniasis (4 cases, 31%), rubella (19 cases, 27%) and typhus fever (32 cases, 18%), filariasis had no incidences in both years, and the diseases with obvious reported case decreases were HFMD (26 506 cases, 23%). other infectious diarrhea (5 628 cases, 6%) and mumps (523 cases, 4%). No death caused by class C communicable diseases was reported, same to the last month and a decrease of 3 deaths compared with the same period in 2020 (3 deaths).