Intrinsic host susceptibility among multiple species to intranasal SARS-CoV-2 identifies diverse virological, biodistribution and pathological outcomes.

SARS-CoV-2 exhibits a diverse host species range with variable outcomes, enabling differential host susceptibility studies to assess suitability for pre-clinical countermeasure and pathogenesis studies. Baseline virological, molecular and pathological outcomes were determined among multiple species-one Old World non-human primate (NHP) species (cynomolgus macaques), two New World NHP species (red-bellied tamarins; common marmosets) and Syrian hamsters-following single-dose, atraumatic intranasal administration of SARS-CoV-2/Victoria-01. After serial sacrifice 2, 10 and 28-days post-infection (dpi), hamsters and cynomolgus macaques displayed differential virus biodistribution across respiratory, gastrointestinal and cardiovascular systems. Uniquely, New World tamarins, unlike marmosets, exhibited high levels of acute upper airway infection, infectious virus recovery associated with mild lung pathology representing a host previously unrecognized as susceptible to SARS-CoV-2. Across all species, lung pathology was identified post-clearance of virus shedding (antigen/RNA), with an association of virus particles within replication organelles in lung sections analysed by electron microscopy. Disrupted cell ultrastructure and lung architecture, including abnormal morphology of mitochondria 10-28 dpi, represented on-going pathophysiological consequences of SARS-CoV-2 in predominantly asymptomatic hosts. Infection kinetics and host pathology comparators using standardized methodologies enables model selection to bridge differential outcomes within upper and lower respiratory tracts and elucidate longer-term consequences of asymptomatic SARS-CoV-2 infection.

Incidence of Guillain-Barré syndrome following SARS-CoV-2 immunization: Analysis of a nationwide registry of recipients of 81 million doses of seven vaccines.

BACKGROUND AND PURPOSE: Information on Guillain-Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS-CoV-2 remains scarce. We aimed to report GBS incidence as an AEFI among adult (≥18 years) recipients of 81,842,426 doses of seven anti-SARS-CoV-2 vaccines between December 24, 2020, and October 29, 2021, in Mexico. METHODS: Cases were retrospectively collected through passive epidemiological surveillance. The overall observed incidence was calculated according to the total number of administered doses. Vaccines were analyzed individually and by vector as mRNA-based (mRNA-1273 and BNT162b2), adenovirus-vectored (ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, and Ad26.COV2-S), and inactivated whole-virion-vectored (CoronaVac) vaccines. RESULTS: We identified 97 patients (52 males [53.6%]; median [interquartile range] age 44 [33-60] years), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97-1.45), with incidence higher among Ad26.COV2-S (3.86/1,000,000 doses, 95% CI 1.50-9.93) and BNT162b2 recipients (1.92/1,00,000 doses, 95% CI 1.36-2.71). The interval (interquartile range) from vaccination to GBS symptom onset was 10 (3-17) days. Preceding diarrhea was reported in 21 patients (21.6%) and mild COVID-19 in four more (4.1%). Only 18 patients were tested for Campylobacter jejuni (positive in 16 [88.9%]). Electrophysiological examinations were performed in 76 patients (78.4%; axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar across the platforms. On admission, 91.8% had a GBS disability score ≥3. Seventy-five patients (77.3%) received intravenous immunoglobulin, received seven plasma exchange (7.2%), and 15 (15.5%) were treated conservatively. Ten patients (10.3%) died, and 79.1% of survivors were unable to walk independently. CONCLUSIONS: Guillain-Barré syndrome was an extremely infrequent AEFI against SARS-CoV-2. The protection provided by these vaccines outweighs the risk of developing GBS.

Transient sensory symptoms among first-dose recipients of the BNT162b2 mRNA COVID-19 vaccine: A case-control study.

mRNA-based COVID-19 vaccines are effective; however, persistent vaccine hesitancy is partly due to a misperception of their potential adverse events. Non-specific sensory symptoms (NSSS) following immunization are thought to be mediated by stress-related responses. In this case-control study, we evaluated NSSS from a cohort of 7,812,845 BNT162b2 first-dose recipients, of whom 10,929 reported an adverse event following immunization (AEFI). We found an overall frequency of 3.4% (377 cases) or 4.8 cases per 100,000 doses administered. Anatomically, the arms (61%) and face/neck region (36.2%) were the most commonly affected sites. The control group had significantly higher rates of reactogenicity-associated symptoms, suggesting that NSSS are reactogenicity-independent; in multivariable analysis, healthcare workers reported sensory symptoms less frequently (aOR 0.54; 95% CI 0.40-0.72;p < 0.001). This is the first study describing the topography and associated factors for developing NSSS among BNT162b2 recipients. The benign nature of these symptoms may help dissipate hesitation towards this vaccine.

COVID-IRS: A novel predictive score for risk of invasive mechanical ventilation in patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a systemic disease that can rapidly progress into acute respiratory failure and death. Timely identification of these patients is crucial for a proper administration of health-care resources. OBJECTIVE: To develop a predictive score that estimates the risk of invasive mechanical ventilation (IMV) among patients with COVID-19. STUDY DESIGN: Retrospective cohort study of 401 COVID-19 patients diagnosed from March 12, to August 10, 2020. The score development cohort comprised 211 patients (52.62% of total sample) whereas the validation cohort included 190 patients (47.38% of total sample). We divided participants according to the need of invasive mechanical ventilation (IMV) and looked for potential predictive variables. RESULTS: We developed two predictive scores, one based on Interleukin-6 (IL-6) and the other one on the Neutrophil/Lymphocyte ratio (NLR), using the following variables: respiratory rate, SpO2/FiO2 ratio and lactic dehydrogenase (LDH). The area under the curve (AUC) in the development cohort was 0.877 (0.823-0.931) using the NLR based score and 0.891 (0.843-0.939) using the IL-6 based score. When compared with other similar scores developed for the prediction of adverse outcomes in COVID-19, the COVID-IRS scores proved to be superior in the prediction of IMV. CONCLUSION: The COVID-IRS scores accurately predict the need for mechanical ventilation in COVID-19 patients using readily available variables taken upon admission. More studies testing the applicability of COVID-IRS in other centers and populations, as well as its performance as a triage tool for COVID-19 patients are needed.