As the COVID-19 pandemic continues, countries around the world are switching toward vaccinations and boosters to combat the pandemic. However, waning immunity against SARS-CoV-2 wild-type (WT) and ...variants have been widely reported. Booster vaccinations have shown to be able to increase immunological protection against new variants; however, the protection observed appears to decrease quickly over time suggesting a second booster shot may be appropriate. Moreover, heterogeneity and waning of the immune response at the individual level was observed suggesting a more personalized vaccination approach should be considered. To evaluate such a personalized strategy, it is important to have the ability to rapidly evaluate the level of neutralizing antibody (nAbs) response against variants at the individual level and ideally at a point of care setting. Here, we applied the recently developed cellulose pulled-down virus neutralization test (cpVNT) to rapidly assess individual nAb levels to WT and variants of concerns in response to booster vaccination. Our findings confirmed significant heterogeneity of nAb responses against a panel of SARS-CoV-2 variants, and indicated a strong increase in nAb response against variants of concern (VOCs) upon booster vaccination. For instance, the nAb response against current predominant omicron variant was observed with medians of 88.1% (
= 6, 95% CI = 73.2% to 96.2%) within 1-month postbooster and 70.7% (
= 22, 95% CI = 66.4% to 81.8%) 3 months postbooster. Our data show a point of care (POC) test focusing on nAb response levels against VOCs can guide decisions on the potential need for booster vaccinations at individual level. Importantly, it also suggests the current booster vaccines only give a transient protective response against some VOC and new more targeted formulations of a booster vaccine against specific VOC may need to be developed in the future.
Vaccination against SARS-CoV-2 induces protection through production of neutralization antibodies (nAb). The level of nAb is a major indicator of immunity against SARS-CoV-2 infection. We developed a rapid point-of-care test that can monitor the nAb level from a drop of finger stick blood. Here, we have implemented the test to monitor individual nAb level against wild-type and variants of SARS-CoV-2 at various time points of vaccination, including post-second-dose vaccination and postbooster vaccination. Huge diversity of nAb levels were observed among individuals as well as increment in nAb levels especially against Omicron variant after booster vaccination. This study evaluated the performance of this point-of-care test for personalized nAb response tracking. It verifies the potential of using a rapid nAb test to guide future vaccination regimens at both the individual and population level.
There is clinical need for a quantifiable point‐of‐care (PoC) SARS‐CoV‐2 neutralizing antibody (nAb) test that is adaptable with the pandemic's changing landscape. Here, we present a rapid and ...semi‐quantitative nAb test that uses finger stick or venous blood to assess the nAb response of vaccinated population against wild‐type (WT), alpha, beta, gamma, and delta variant RBDs. It captures a clinically relevant range of nAb levels, and effectively differentiates prevaccination, post first dose, and post second dose vaccination samples within 10 min. The data observed against alpha, beta, gamma, and delta variants agrees with published results evaluated in established serology tests. Finally, our test revealed a substantial reduction in nAb level for beta, gamma, and delta variants between early BNT162b2 vaccination group (within 3 months) and later vaccination group (post 3 months). This test is highly suited for PoC settings and provides an insightful nAb response in a postvaccinated population.
Background.
Immunocompromised individuals have been excluded from landmark studies of messenger RNA vaccinations for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In such ...patients, the response to vaccination may be blunted and may wane more quickly compared with immunocompetent patients. We studied the factors associated with decreased antibody response to SARS-CoV-2 vaccination and risk factors for subsequent breakthrough infections in liver transplant (LT) patients undergoing coronavirus disease 2019 vaccination with at least 2 doses of messenger RNA vaccine from April 28, 2021, to April 28, 2022.
Methods.
All LT recipients received at least 2 doses of the BNT162b2 (Pfizer BioNTech) vaccine 21 d apart. We measured the antibody response against the SARS-CoV-2 spike protein using the Roche Elecsys immunoassay to the receptor-binding domain of the SARS-CoV-2 spike protein, and the presence of neutralizing antibodies was measured by the surrogate virus neutralization test (cPass) before first and second doses of vaccination and also between 2 and 3 mo after the second dose of vaccination.
Results.
Ninety-three LT recipients who received 2 doses of BNT162b2 were included in the analysis. The mean time from LT was 110 ± 154 mo. After 2-dose vaccination, 38.7% of LT recipients (36/93) were vaccine nonresponders on the cPass assay compared with 20.4% (19/93) on the Roche S assay. On multivariable analysis, increased age and increased tacrolimus trough were found to be associated with poor neutralizing antibody response (
P
= 0.038 and 0.022, respectively). The use of antimetabolite therapy in conjunction with tacrolimus approached statistical significance (odds ratio 0.21; 95% confidence interval, 0.180-3.72;
P
= 0.062). Breakthrough infection occurred in 18 of 88 LT recipients (20.4%). Female gender was independently associated with breakthrough infections (
P
< 0.001).
Conclusions.
Among LT recipients, older age and higher tacrolimus trough levels were associated with poorer immune response to 2-dose SARS-CoV-2 vaccination. Further studies are needed to assess variables associated with breakthrough infections and, hence, who should be prioritized for booster vaccination.
By estimating N95 respirator demand based on simulated epidemics, we aim to assist planning efforts requiring estimations of respirator demand for the healthcare system to continue operating safely ...in the coming months.
We assess respiratory needs over the course of mild, moderate and severe epidemic scenarios within Singapore as a case study using a transmission dynamic model. The number of respirators required within the respiratory isolation wards and intensive care units was estimated over the course of the epidemic. We also considered single-use, extended-use and prolonged-use strategies for N95 respirators for use by healthcare workers treating suspected but negative (misclassified) or confirmed COVID-19 patients.
Depending on the confirmed to misclassified case ratio, from 1:0 to 1:10, a range of 117.1 million to 1.1 billion masks are required for single-use. This decreases to 71.6-784.4 million for extended-use and 12.8-148.2 million for prolonged-use, representing a 31.8-38.9% and 86.5-89.1% reduction, respectively.
An extended-use policy should be considered when short-term supply chains are strained but planning measures are in place to ensure long-term availability. With severe shortage expectations from a severe epidemic, as some European countries have experienced, prolonged use is necessary to prolong supply.
Objective
Despite the high vaccine efficacy of mRNA COVID‐19 vaccines, there are individuals who developed excessive reactogenic and/or allergic responses after the first mRNA dose and were ...considered ineligible for further mRNA doses. CoronaVac, an inactivated SARS‐CoV‐2 vaccine, is recommended in Singapore as an alternative.
Methods
Individuals, ineligible for further mRNA vaccines (BNT162b2 or mRNA‐1273) because of excessive reactive responses to prime mRNA vaccination, were recruited and offered two doses of CoronaVac as booster vaccination 38–224 days post their mRNA vaccine dose. Individuals who did not develop any excessive reactive responses after the prime mRNA vaccination were also recruited and given another mRNA vaccine as booster vaccination. Blood samples were collected at days 0, 21 and 90 post first CoronaVac dose and mRNA dose, respectively, for analysis.
Results
We showed that two CoronaVac booster doses induced specific immunity in these mRNA vaccine‐primed individuals. Although the spike‐specific antibody response was lower, their memory B cell response against the receptor‐binding domain (RBD) of the spike protein was similar, compared with individuals who received two BNT162b2 injections. The spike‐specific memory T cell response also increased following CoronaVac booster doses. However, specific immunity against the Omicron variant was low, similar to individuals with two BNT162b2 doses.
Conclusion
Our findings showed that while mRNA vaccine‐primed individuals can opt for two subsequent doses of CoronaVac, an additional dose may be necessary to achieve protection, especially against newly emerging immune escape variants such as Omicron.
Individuals, ineligible for further mRNA vaccines because of excessive reactive responses to prime mRNA vaccination, were recruited and offered two doses of CoronaVac as booster vaccination. Individuals who did not develop any excessive reactive responses after the prime mRNA vaccination received another mRNA vaccine as booster vaccination. Blood samples were collected at days 0, 21 and 90 post first CoronaVac dose and mRNA dose, respectively, and the antibody profiles, B and T cell responses, were analysed.
Clinical manifestations, treatment, and outcomes of cutaneous cryptococcosis in solid organ transplant (SOT) recipients are not fully defined. In a prospective cohort comprising 146 SOT recipients ...with cryptococcosis, we describe the presentation, antifungal therapy, and outcome of cutaneous cryptococcal disease. Cutaneous cryptococcosis was documented in 26/146 (17.8%) of the patients and manifested as nodular/mass (34.8%), maculopapule (30.4%), ulcer/pustule/abscess (30.4%), and cellulitis (30.4%) with 65.2% of the skin lesions occurred in the lower extremities. Localized disease developed in 30.8% (8/26), and disseminated disease in 69.2% (18/26) with involvement of the central nervous system (88.9%, 16/18), lung (33.3%, 6/18), or fungemia (55.6%, 10/18). Fluconazole (37.5%) was employed most often for localized and lipid formulations of amphotericin B (61.1%) for disseminated disease. Overall mortality at 90 days was 15.4% (4/26) with 16.7% in disseminated and 12.5% in localized disease (P = 0.78). SOT recipients who died were more likely to have renal failure (75.0% vs. 13.6%, P = 0.028), longer time to onset of disease after transplantation (87.5 vs. 22.6 months, P = 0.023), and abnormal mental status (75% vs. 13.6%, P = 0.028) than those who survived. Cutaneous cryptococcosis represents disseminated disease in most SOT recipients and preferentially involves the extremities. Outcomes with appropriate management were comparable between SOT recipients with localized and disseminated cryptococcosis.
PDF
