COVID‐19 post‐vaccination lymphadenopathy: A review of the use of fine needle aspiration cytology

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Abstract

COVID‐19 vaccine‐associated clinical lymphadenopathy (C19‐LAP) and subclinical lymphadenopathy (SLDI), which are mainly detected by 18F‐FDG PET‐CT, have been observed after the introduction of RNA‐based vaccines during the pandemic. Lymph node (LN) fine needle aspiration cytology (FNAC) has been used to diagnose single cases or small series of SLDI and C19‐LAP. In this review, clinical and LN‐FNAC features of SLDI and C19‐LAP are reported and compared to non‐Covid (NC)‐LAP. A search for studies on C19‐LAP and SLDI histopathology and cytopathology was performed on PubMed and Google Scholar, on 11 January 2023. Reports on LN‐FNAC of C19‐LAP were retrieved. A total of 14 reports, plus one unpublished case of C19‐LAP observed in our institution, diagnosed by LN‐FNAC were included in a pooled analysis and compared to the corresponding histopathological reports. In total, 26 cases were included in this review, with a mean age of 50.5 years. Twenty‐one lymphadenopathies assessed by LN‐FNAC were diagnosed as benign, and three cases as atypical lymphoid hyperplasia; the latter were subsequently confirmed as benign (one by repetition of LN‐FNAC, two by histological control). One case of mediastinal lymphadenopathy in a patient suffering from melanoma was reported as reactive granulomatous inflammation, while one unsuspected case was diagnosed as metastasis from melanoma. In all cases, the cytological diagnoses were confirmed by follow‐up or excisional biopsy. The high diagnostic value of LN‐FNAC in excluding malignant processes was extremely useful in this context and may be particularly valuable when CNB or histological excisions are difficult to perform, as was the case during Covid lockdowns.

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Immunological mechanisms of vaccine-induced protection against COVID-19 in humans

Manish Sadarangani, Arnaud Marchant, Tobias Kollmann (2021)

Most COVID-19 vaccines are designed to elicit immune responses, ideally neutralizing antibodies (NAbs), against the SARS-CoV-2 spike protein. Several vaccines, including mRNA, adenoviral-vectored, protein subunit and whole-cell inactivated virus vaccines, have now reported efficacy in phase III trials and have received emergency approval in many countries. The two mRNA vaccines approved to date show efficacy even after only one dose, when non-NAbs and moderate T helper 1 cell responses are detectable, but almost no NAbs. After a single dose, the adenovirus vaccines elicit polyfunctional antibodies that are capable of mediating virus neutralization and of driving other antibody-dependent effector functions, as well as potent T cell responses. These data suggest that protection may require low levels of NAbs and might involve other immune effector mechanisms including non-NAbs, T cells and innate immune mechanisms. Identifying the mechanisms of protection as well as correlates of protection is crucially important to inform further vaccine development and guide the use of licensed COVID-19 vaccines worldwide. This Progress article summarizes our current understanding of the immune mechanisms of protection induced by the available COVID-19 vaccines. The authors compare vaccine-induced antibody responses following one or two doses of different vaccines and consider the relative importance of neutralizing antibodies for vaccine-mediated protection against SARS-CoV-2.