Durable SARS-CoV-2 B cell immunity after mild or severe disease

Multiple studies have shown loss of severe acute respiratory syndrome coronavirus 2–specific (SARS-CoV-2–specific) antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from coronavirus disease 2019 (COVID-19). However, memory B cells (MBCs) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multidimensional flow cytometric analysis of S protein receptor binding domain–specific (S-RBD–specific) MBCs in cohorts of ambulatory patients with COVID-19 with mild disease (n = 7), and hospitalized patients with moderate to severe disease (n = 7), at a median of 54 days (range, 39–104 days) after symptom onset. We detected S-RBD–specific class-switched MBCs in 13 of 14 participants, failing only in the individual with the lowest plasma levels of anti–S-RBD IgG and neutralizing antibodies. Resting MBCs (rMBCs) made up the largest proportion of S-RBD–specific MBCs in both cohorts. FCRL5, a marker of functional memory on rMBCs, was more dramatically upregulated on S-RBD–specific rMBCs after mild infection than after severe infection. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD–specific, class-switched rMBCs that resemble germinal center–derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell–mediated immunity against SARS-CoV-2 after mild or severe disease.     

First-dose mRNA vaccination is sufficient to reactivate immunological memory to SARS-CoV-2 in subjects who have recovered from COVID-19

The characterization of the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV-2 infection may define current and future clinical practice. To determine the effect of the 2-dose BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (COVID-19–recovered subjects) compared with naive subjects, we evaluated SARS-CoV-2 Spike–specific T and B cell responses, as well as specific IgA, IgG, IgM, and neutralizing antibodies titers in 22 individuals who received the BNT162b2 mRNA COVID-19 vaccine, 11 of whom had a previous history of SARS-CoV-2 infection. Evaluations were performed before vaccination and then weekly until 7 days after second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in COVID-19–recovered subjects without any additional improvement after the second dose. On the contrary, the second dose proved mandatory in naive subjects to further enhance the immune response. These findings were further confirmed at the serological level in a larger cohort of naive (n = 68) and COVID-19–recovered (n = 29) subjects, tested up to 50 days after vaccination. These results question whether a second vaccine injection in COVID-19–recovered subjects is required, and indicate that millions of vaccine doses may be redirected to naive individuals, thus shortening the time to reach herd immunity.     

Antibody response to third and fourth BNT162b2 mRNA booster vaccinations in healthcare workers in Tokyo,Japan

BackgroundBooster vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being promoted worldwide to counter the coronavirus disease 2019 (COVID-19) pandemic. In this study, we analyzed the longitudinal effect of the third BNT162b2 mRNA vaccination on antibody responses in healthcare workers. Additionally, antibody responses induced by the fourth vaccination were analyzed.MethodsThe levels of anti-spike (S) IgG and neutralizing antibody against SARS-CoV-2 were measured at 7 months after the second vaccination (n = 1138), and at 4 (n = 701) and 7 (n = 417) months after the third vaccination using an iFlash 3000 chemiluminescence immunoassay analyzer. Among the 417 participants surveyed at 7 months after the third vaccination, 40 had received the fourth vaccination. A multiple linear regression analysis was performed to clarify which factors were associated with the anti-S IgG and neutralizing antibody. Variables assessed included sex, age, number of days after the second or third vaccination, diagnostic history of COVID-19, and anti-nucleocapsid (N) IgG level.ResultsAt 7 months after the third vaccination, antibody responses were significantly higher than those at the same time after the second vaccination. Unlike the second vaccination, age had no effect on the antibody responses induced by the third vaccination. Furthermore, the fourth vaccination resulted in a further increase in antibody responses. The multiple linear regression analysis identified anti-N IgG level, presumably associated with infection, as a factor associated with antibody responses.ConclusionsOur findings showed that BNT162b2 booster vaccinations increased and sustained the antibody responses against SARS-CoV-2.     

Antibody responses and SARS-CoV-2 infection after BNT162b2 mRNA booster vaccination among healthcare workers in Japan

IntroductionVaccine effectiveness against SARS-CoV-2 infections decreases due to waning immunity, and booster vaccination was therefore introduced. We estimated the anti-spike antibody (AS-ab) recovery by booster vaccination and analyzed the risk factors for SARS-CoV-2 infections.MethodsThe subjects were health care workers (HCWs) in a Chiba University Hospital vaccination cohort. They had received two doses of vaccine (BNT162b2) and a booster vaccine (BNT162b2). We retrospectively analyzed AS-ab titers and watched out for SARS-CoV-2 infection for 90 days following booster vaccination.ResultsAS-ab titer eight months after two-dose vaccinations had decreased to as low as 587 U/mL (median, IQR (interquartile range) 360–896). AS-ab titer had then increased to 22471 U/mL (15761–32622) three weeks after booster vaccination. There were no significant differences among age groups.A total of 1708 HCWs were analyzed for SARS-CoV-2 infection, and 48 of them proved positive. SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 1.8% and 4.0%, respectively, and were not significant. However, when restricted to those 20–29 years old, SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 2.9% and 13.6%, respectively (p = 0.04). After multivariate logistic regression, COVID-19 wards (adjusted odds ratio (aOR):2.9, 95% confidence interval (CI) 1.5–5.6) and those aged 20–49 years (aOR:9.7, 95%CI 1.3–71.2) were risk factors for SARS-CoV-2 infection.ConclusionsBooster vaccination induced the recovery of AS-ab titers. Risk factors for SARS-CoV-2 infection were HCWs of COVID-19 wards and those aged 20–49 years. Increased vaccination coverage, together with implementing infection control, remains the primary means of preventing HCWs from SARS-CoV-2 infection.     

Features of antibody responses after SARS-COV-2 infection in healthcare workers in the first wave of COVID-19 pandemic in Mexico City

ObjectiveTo investigate the antibody response to SARS-CoV-2 and identify associated factors in frontline and second-line healthcare workers (HCWs) at a large hospital in Mexico City during the first wave of COVID-19 pandemic.MethodsThis was a cross-sectional study of HCWs returning to work following mandatory isolation after recovering from COVID-19. Immunoglobulin (Ig) M and IgG antibodies elicited by SARS-CoV-2 were semiquantitatively measured using densitometric analysis of band intensities in lateral flow assay (LFA) devices. The mean pixel intensity (dots-per-inch [dpi]) of each band on the LFA was considered a measure of antibody titre.ResultsOf the 111 HCWs involved in the study, antibody responses were detected in 73/111 (66%) participants. Severe COVID symptoms was associated with old age. No differences in IgM intensity were observed between men and women, but IgG intensity was significantly higher in men than in women. Second-line HCWs produced a higher IgG intensity than firstline HCWs. The IgG intensity was high in severe cases.ConclusionsFor HCWs who may acquire SARS-CoV-2 infection, it is necessary to establish a routine program for detection of the virus to avoid risk of infection and spread of COVID-19.     

Epidemiological study using IgM and IgG antibody titers against SARS-CoV-2 in The University of Tokyo,Japan (UT-CATS)

IntroductionThe worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to date. Given that some of the patients with coronavirus disease 2019 (COVID-19) are asymptomatic, antibody tests are useful to determine whether there is a previous infection with SARS-CoV-2. In this study, we measured IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects in The University of Tokyo, Japan.MethodsFrom June 2020, we recruited participants, who were students, staff, and faculty members of The University of Tokyo in the project named The University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS). Following blood sample collection, participants were required to answer an online questionnaire about their social and health information. We measured IgG and IgM titers against SARS-CoV-2 using iFlash-SARS-CoV-2 IgM and IgG detection kit which applies a chemiluminescent immunoassay (CLIA) for the qualitative detection.ResultsThere were 6609 volunteers in this study. After setting the cutoff value at 10 AU/mL, 32 (0.48%) were positive for IgG and 16 (0.24%) for IgM. Of six participants with a history of COVID-19, five were positive for IgG, whereas all were negative for IgM. The median titer of IgG was 0.40 AU/mL and 0.39 AU/mL for IgM. Both IgG and IgM titers were affected by gender, age, smoking status, and comorbidities.ConclusionsPositive rates of IgG and IgM titers were relatively low in our university. Serum levels of these antibodies were affected by several factors, which might affect the clinical course of COVID-19.     

Does common cold coronavirus infection protect against severe SARS-CoV-2 disease?

The coronavirus disease 2019 (COVID-19) pandemic continues to cause morbidity and mortality. Since SARS coronavirus 2 (SARS-CoV-2) was identified as the cause for COVID-19, some have questioned whether exposure to seasonal common cold coronaviruses (CCCs) could provide tangible protection against SARS-CoV-2 infection or disease. In this issue of the JCI, Sagar et al. examined SARS-CoV-2 infections and outcomes of patients who had previously tested positive or negative for CCC infection (CCC⁺ or CCC^–) by a comprehensive respiratory panel using PCR. No differences were seen between groups in terms of susceptibility to SARS-CoV-2 infection. However, hospitalized patients with a documented history of CCC infection had lower rates of intensive care unit (ICU) admissions and higher rates of survival than hospitalized CCC^– patients. While these findings are associative and not causative, they highlight evidence suggesting that previous CCC infection may influence the disease course of SARS-CoV-2 infection.     

Comparison of SARS-CoV-2 IgM and IgG seroconversion profiles among hospitalized patients in two US cities

The clinical and public health utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic testing requires a better understanding of the dynamics of the humoral response to infection. To track seroconversion of IgG and IgM antibodies in patients with SARS-CoV-2 infection and its association with patient and clinical factors and outcomes. Residual patient specimens were analyzed on the Abbott ARCHITECT i2000 instrument using the Abbott SARS-CoV-2 IgG assay and prototype SARS-CoV-2 IgM assay. Age, sex, comorbidities, symptom onset date, mortality, and specimen collection date were obtained from electronic medical records. Three hundred fifty-nine longitudinal samples were collected from 89 hospitalized patients 0 to 82 days postsymptom onset. Of all, 51.7% of the patients developed IgG and IgM antibodies simultaneously; 32.8% seroconverted for IgM before IgG. On average, patients seroconverted for IgG by 8 days and for IgM by 7 days postsymptom onset. All patients achieved IgG seropositivity by 19 days and IgM seropositivity by 17 days. Median time to IgG and IgM seroconversion was prolonged and initial levels of IgG were lower in immunocompromised patients and patients <65 years of age compared to immune competent patients and those ≥65 years of age. Immunocompromised patients also had persistently lower levels of IgM that peaked on day 17.6 and decreased thereafter compared to immune competent patients. IgM seroconversion in patients who died reached significantly higher levels later after symptom onset than in those who recovered. SARS-CoV-2 infected patients have similar time to seroconversion for IgG and IgM. However, differences in immune status and age alter time to seroconversion. These results may help guide serologic testing application in COVID-19 management.     

SARS-CoV-2 infection and vaccination trigger long-lived B and CD4+ T lymphocytes with implications for booster strategies

BACKGROUNDImmunization against SARS-CoV-2, the causative agent of COVID-19, occurs via natural infection or vaccination. However, it is currently unknown how long infection- or vaccination-induced immunological memory will last.METHODSWe performed a longitudinal evaluation of immunological memory to SARS-CoV-2 up to 1 year after infection and following mRNA vaccination in naive individuals and individuals recovered from COVID-19 infection.RESULTSWe found that memory cells are still detectable 8 months after vaccination, while antibody levels decline significantly, especially in naive individuals. We also found that a booster injection is efficacious in reactivating immunological memory to spike protein in naive individuals, whereas it was ineffective in previously SARS-CoV-2–infected individuals. Finally, we observed a similar kinetics of decay of humoral and cellular immunity to SARS-CoV-2 up to 1 year following natural infection in a cohort of unvaccinated individuals.CONCLUSIONShort-term persistence of humoral immunity, together with the reduced neutralization capacity versus the currently prevailing SARS-CoV-2 variants, may account for reinfections and breakthrough infections. Long-lived memory B and CD4⁺ T cells may protect from severe disease development. In naive individuals, a booster dose restored optimal anti-spike immunity, whereas the needs for vaccinated individuals who have recovered from COVID-19 have yet to be defined.FUNDINGThis study was supported by funds to the Department of Experimental and Clinical Medicine, University of Florence (Project Excellence Departments 2018–2022), the University of Florence (project RICTD2122), the Italian Ministry of Health (COVID-2020-12371849), and the region of Tuscany (TagSARS CoV 2).     

Relationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection

T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2–specific (SARS-CoV-2–specific) CD4⁺ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non–COVID-19 patients. We showed that SARS-CoV-2–specific CD4⁺ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1–mediated CD4⁺ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2–specific CD4⁺ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis–specific CD4⁺ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2–specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.     

Evaluation of residual humoral immune response against SARS-CoV-2 by a surrogate virus neutralization test (sVNT) 9 months after BNT162b2 primary vaccination

The humoral response to SARS-CoV-2 vaccination has shown to be temporary, although may be more prolonged in vaccinated individuals with a history of natural infection. We aimed to study the residual humoral response and the correlation between anti-Receptor Binding Domain (RBD) IgG levels and antibody neutralizing capacity in a population of health care workers (HCWs) after 9 months from COVID-19 vaccination.In this cross-sectional study, plasma samples were screened for anti-RBD IgG using a quantitative method. The neutralizing capacity for each sample was estimated by means of a surrogate virus neutralizing test (sVNT) and results expressed as the percentage of inhibition (%IH) of the interaction between RBD and the angiotensin-converting enzyme.Samples of 274 HCWs (227 SARS-CoV-2 naïve and 47 SARS-CoV-2 experienced) were tested. The median level of anti-RBD IgG was significantly higher in SARS-CoV-2 experienced than in naïve HCWs: 2673.2 AU/mL versus 610.9 AU/mL, respectively (p <0.001). Samples of SARS-CoV-2 experienced subjects also showed higher neutralizing capacity as compared to naïve subjects: median %IH = 81.20% versus 38.55%, respectively; p <0.001. A quantitative correlation between anti-RBD Ab and inhibition activity levels was observed (Spearman's rho = 0.89, p <0.001): the optimal cut-off correlating with high neutralization was estimated to be 1236.1 AU/mL (sensitivity 96.8%, specificity 91.9%; AUC 0.979).Anti-SARS-CoV-2 hybrid immunity elicited by a combination of vaccination and infection confers higher anti-RBD IgG levels and higher neutralizing capacity than vaccination alone, likely providing better protection against COVID-19.     

Factors associated with high antibody titer following coronavirus disease among 581 convalescent plasma donors: A single-center cross-sectional study in Japan

IntroductionThe ability to predict which patients with a history of coronavirus disease (COVID-19) will exhibit a high antibody titer is necessary for more efficient screening of potential convalescent plasma donors. We aimed to identify factors associated with a high immunoglobulin G (IgG) titer in Japanese convalescent plasma donors after COVID-19.MethodsThis cross-sectional study included volunteers undergoing screening for convalescent plasma donation after COVID-19. Serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-protein IgG antibodies were measured using a high-sensitivity chemiluminescence enzyme immunoassay.ResultsIgG antibodies were measured in 581 patients, 534 of whom had full information of selected independent variables. Multiple linear regression analysis revealed that increasing age (1.037 [1,025, 1.048]), days from symptom onset to sampling (0.997 [0.995, 0.998]), fever (1.664 [1.226, 2.259]), systemic corticosteroid use during SARS-CoV-2 infection (2.382 [1.576, 3.601]), and blood type AB (1.478 [1.032, 2.117]) predict antibody titer.ConclusionOlder participants, those who experienced fever during infection, those treated with systemic corticosteroids during infection, those from whom samples were obtained earlier after symptom onset, and those with blood type AB are the best candidates for convalescent plasma donation. Therefore, these factors should be incorporated into the screening criteria for convalescent plasma donation after SARS-CoV-2 infection.     

Multifocal motor neuropathy after SARS-CoV-2 vaccination: a causal or coincidental association?

Multifocal motor neuropathy (MMN) is an immune-mediated and acquired demyelinating motor polyneuropathy. Several cases of polyneuropathy associated with severe acquired respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination have been reported. However, MMN has not been reported as a complication of SARS-CoV-2 vaccination. In this study, we report a case of MMN with progressive muscle weakness following the second dose of the Pfizer-BioNTech mRNA vaccine. It was diagnosed by clinical evaluation and electroneuromyography. SARS-CoV-2 vaccination is increasing rapidly all over the world. Some cases of polyneuropathy, especially Guillain–Barré syndrome, have been reported after vaccination. This is the first case report of MMN after SARS-CoV-2 vaccination.     

Rapid Serological Tests for SARS-CoV-2: Diagnostic Performance of 4 Commercial Assays

ObjectiveTo assess the diagnostic performance of lateral flow immunochromatographic assays (LFAs) of 4 different manufacturers to identify SARS-CoV-2 antibodies (IgM, IgG, or total), comparing them with the nucleic acid amplification test (NAAT) or the clinical defined test (definite or probable SARS-CoV-2 infection, respectively).MethodsOne hundred nineteen serum samples were randomly selected by convenience and distributed in the following groups: (1) group with SARS-CoV-2 infection (n = 82; RT-qPCR positive [definite, n = 70] and probable [n = 12]); (2) other diseases (n = 27; other viruses identified [n = 8] and SARS of other etiologies [n = 19]); and (3) healthy control group (n = 10). LFAs of 4 manufacturers were compared: MedTest Coronavirus (COVID-19) IgG/IgM (MedLevensohn, Brazil); COVID-19 IgG/IgM ECO Test (Ecodiagnóstica, Brazil); Camtech COVID-19 IgM/IgG Rapid Test Kit (Camtech Diagnostics Pte Ltd, Singapore); and 1-Step COVID-19 Test for total antibodies (Guangzhou Wondfo Biotech Co., China).ResultsThe 4 tests studied showed high diagnostic performance characteristics for the diagnoses of definite or probable SARS-CoV-2 infection. The best measures were for the Wondfo test: sensitivity (86.59%; 95% CI: 77.26–93.11%), specificity (100%; 90.51–100%), DOR (257; 60–1,008), LR+ (33.43; 4.82–231.85), LR− (0.13; 0.08–0.23), accuracy (90.76%; 84.06–95.29%), and Matthews correlation coefficient (MCC) 0.82. Although considering only the probable SARS-CoV-2 infection (PCR−) cases, all the kits studied showed limited values.ConclusionOur data demonstrate the excellent performance of LFA for the diagnoses of definite or probable SARS-CoV-2 infection. There was substantial heterogeneity in sensitivities of IgM and IgG antibodies among the different kits. LFA tests cannot replace molecular diagnostics but should be used as an additional screening tool.     

The demographic and serological characteristics of COVID-19 convalescent plasma donors: Identification of basic criteria for optimal donor selection

Background and ObjectivesConvalescent plasma has attracted significant attention as a therapeutic option against infectious agents for more than a century. In March 2020, the use of Convalescent COVID-19 plasma (CCP) as a new research drug for COVID-19 treatment was approved by the FDA. The development of SARS-CoV-2 IgG antibodies following infection or vaccination is likely to be essential to provide adequate immunity for the population to halt the COVID19 pandemic. This study aimed to identify the criteria that would be used to determine the most appropriate CCP donors with the highest effective antiviral antibody titers.Materials and MethodsIn this prospective cohort, univariate analyses and multivariate regression analyses were performed to evaluate the relationship between characteristics of 11949 CCP donors and COVID-19 disease severity prior to donation with antibody titers estimated using ELISA technique and rapid tests.ResultsThe antibody titer was measured among 8206 (68.7 %) donors. Elderly male and nulliparous female CCP donors who resided in the areas with high load of virus had positive ELISA and rapid test results as well as high levels of SARS-CoV-2 IgG antibodies titer. Moreover, the long hospital stay and elderly donors were the variables associated with high levels of SARS-CoV-2 IgG antibodies.ConclusionThis study suggests that nulliparous female and male donors with positive rapid tests who resided in areas with a higher prevalence of SARS-CoV-2, with more than 40 years of age and long hospitalization time can be the preferred donors for CCP donation.     

The Incidence of Diabetes Among 2,777,768 Veterans With and Without Recent SARS-CoV-2 Infection

OBJECTIVETo examine associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/coronavirus disease 2019 with incident diabetes.RESEARCH DESIGN AND METHODSWe conducted a retrospective cohort study using Veterans Health Administration data. We defined all patients without preexisting diabetes with one or more nasal swabs positive for SARS-CoV-2 (1 March 2020–10 March 2021; n = 126,710) as exposed and those with no positive swab and one or more laboratory tests (1 March 2020–31 March 2021; n = 2,651,058) as unexposed. The index date for patients exposed was the date of first positive swab and for patients unexposed a random date during the month of the qualifying laboratory test. We fit sex-stratified logistic regression models examining associations of SARS-CoV-2 with incident diabetes within 120 days and all follow-up time through 1 June 2021. A subgroup analysis was performed among hospitalized subjects only to help equalize laboratory surveillance.RESULTSSARS-CoV-2 was associated with higher risk of incident diabetes, compared with no positive tests, among men (120 days, odds ratio [OR] 2.56 [95% CI 2.32–2.83]; all time, 1.95 [1.80–2.12]) but not women (120 days, 1.21 [0.88–1.68]; all time, 1.04 [0.82–1.31]). Among hospitalized participants, SARS-CoV-2 was associated with higher risk of diabetes at 120 days and at the end of follow-up in men (OR 1.42 [95% CI 1.22–1.65] and 1.32 [1.16–1.50], respectively) but not women (0.72 [0.34–1.52] and 0.80 [0.44–1.45]). Sex ∗ SARS-CoV-2 interaction P values were all <0.1.CONCLUSIONSSARS-CoV-2 is associated with higher risk of incident diabetes in men but not in women even after greater surveillance related to hospitalization is accounted for.     

Bell’s palsy after inactivated COVID-19 vaccination in a patient with history of recurrent Bell’s palsy: A case report

BACKGROUNDWith rapid and extensive administration of inactivated coronavirus disease 2019 (COVID-19) vaccine to the general population in China, it is crucial for clinicians to recognize neurological complications or other side effects associated with COVID-19 vaccination.CASE SUMMARYHere we report the first case of Bell’s palsy after the first dose of inactivated COVID-19 vaccine in China. The patient was a 36-year-old woman with a past history of Bell’s palsy. Two days after receiving the first dose of the Sinovac Life Sciences inactivated COVID-19 vaccine, the patient developed right-side Bell’s palsy and binoculus keratoconjunctivitis. Prednisone, artificial tears and fluorometholone eye drops were applied. The patient’s symptoms began to improve by day 7 and resolved by day 54.CONCLUSIONAs mRNA COVID-19 vaccine trials reported cases of Bell’s palsy as adverse events, we should pay attention to the occurrence of Bell’s palsy after inactivated COVID-19 vaccination. A history of Bell’s palsy, rapid increase of immunoglobulin M and immunoglobin G-specific antibodies to severe acute respiratory syndrome coronavirus 2 may be risk factors for Bell‘s palsy after COVID-19 vaccination.     

A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia

BackgroundAntibody-based strategies for COVID-19 have shown promise in prevention and treatment of early disease. COVID-19 convalescent plasma (CCP) has been widely used but results from randomized trials supporting its benefit in hospitalized patients with pneumonia are limited. Here, we assess the efficacy of CCP in severely ill, hospitalized adults with COVID-19 pneumonia.MethodsWe performed a randomized control trial (PennCCP2), with 80 adults hospitalized with COVID-19 pneumonia, comparing up to 2 units of locally sourced CCP plus standard care versus standard care alone. The primary efficacy endpoint was comparison of a clinical severity score. Key secondary outcomes include 14- and 28-day mortality, 14- and 28-day maximum 8-point WHO ordinal score (WHO8) score, duration of supplemental oxygenation or mechanical ventilation, respiratory SARS-CoV-2 RNA, and anti–SARS-CoV-2 antibodies.ResultsEighty hospitalized adults with confirmed COVID-19 pneumonia were enrolled at median day 6 of symptoms and day 1 of hospitalization; 60% were anti–SARS-CoV-2 antibody seronegative. Participants had a median of 3 comorbidities, including risk factors for severe COVID-19 and immunosuppression. CCP treatment was safe and conferred significant benefit by clinical severity score (median [MED] and interquartile range [IQR] 10 [5.5–30] vs. 7 [2.75–12.25], P = 0.037) and 28-day mortality (n = 10, 26% vs. n = 2, 5%; P = 0.013). All other prespecified outcome measures showed weak evidence toward benefit of CCP.ConclusionTwo units of locally sourced CCP administered early in hospitalization to majority seronegative participants conferred a significant benefit in clinical severity score and 28-day mortality. Results suggest CCP may benefit select populations, especially those with comorbidities who are treated early.Trial RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT04397757","term_id":"NCT04397757"}}NCT04397757.FundingUniversity of Pennsylvania.     

Potential relationships between COVID-19 and the thyroid gland: an update

In this review, I aim to provide a complete overview of recent advances in knowledge regarding severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)-induced thyroid dysfunction. I discuss the findings regarding the role of SARS-CoV-2 in the development of thyroid dysfunction, including subacute thyroiditis, Graves’ disease, non-thyroidal illness, thyrotoxicosis and Hashimoto’s thyroiditis during and subsequent to coronavirus disease 2019 (COVID-19). The thyroid gland and the entire hypothalamic–pituitary–thyroid (HPT) axis may represent key targets of SARS-CoV-2. Thyroid dysfunction during and subsequent to COVID-19 has been documented in clinical studies and is usually reversible. Most of the thyroid disorders, including Graves’ disease, euthyroid sick syndrome, Hashimoto’s thyroiditis and subacute thyroiditis, have been documented as sequelae to COVID-19, and the SARS-CoV-2 virus has been implicated in the aetiology of each. COVID-19 has been suggested to trigger the activation of pre-existing thyroid disease or autoimmunity. Furthermore, patients with uncontrolled thyrotoxicosis are at risk of SARS-CoV-2 infection-related consequences. Because of the neutropenia caused by antithyroid medications, which may obscure the signs of COVID-19, this group of patients should receive special attention. It is suggested that thyroid dysfunction during COVID-19 is caused by direct infection of the thyroid or “cytokine storm”-mediated autoimmune effects on the thyroid.