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.

Humoral response to different SARS-CoV-2 vaccines in orthotopic liver transplant recipients.

BACKGROUND: The safety and efficacy data of the different types of available vaccines is still needed. The goal of the present analysis was to evaluate the humoral response to the COVID-19 vaccines in orthotopic liver transplant (OLT) recipients. METHODS: Participants were included from February to September 2021. No prioritized vaccination roll call applied for OLT patients. Controls were otherwise healthy people. Blood samples were drawn after 15 days of the complete vaccine doses. The samples were analyzed according to the manufacturer's instructions using the Liaison XL platform from DiaSorin (DiaSorin S.p.A., Italy), and SARS-COV-2 IgG II Quant (Abbott Diagnostics, IL, USA). RESULTS: A total of 187 participants (133 OLT, 54 controls, median age: 60 years, 58.8% women) were included for the analysis; 74.3% had at least one comorbidity. The serologic response in OLT patients was lower than in controls (median 549 AU/mL vs. 3450 AU/mL, respectively; p = 0.001). A positive humoral response was found in 133 OLT individuals: 89.2% with BNT162b2 (Pfizer-BioNTech), 60% ChAdOx1 nCOV-19 (Oxford-AstraZeneca), 76.9% with CoronaVac (Sinovac, Life Sciences, China), 55.6% Ad5-nCov (Cansino, Biologics), 68.2% Gam-COVID-Vac (Sputnik V) and 100% with mRNA-1273. In controls the serological response was 100%, except for Cansino (75%). In a multivariable model, personal history of COVID-19 and BNT162b2 inoculation were associated with the serologic response, while the use of prednisone (vs. other immunosuppressants) reduced this response. CONCLUSION: The serologic response to COVID-19 vaccines in OLT patients is lower than in healthy controls. The BNT162b2 vaccine was associated with a higher serologic response.

Psychological and Psychiatric Events Following Immunization with Five Different Vaccines against SARS-CoV-2.

BACKGROUND: Despite the high number of vaccines administered against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, the information on the psychological/psychiatric adverse events following immunization (AEFI) with these newly developed vaccines remains scarce. OBJECTIVE: To describe the frequency of psychological/psychiatric symptoms among recipients of five different anti-SARS-CoV-2 vaccines and to explore the factors associated with their development reported in the nationwide Mexican registry of AEFI against SARS-CoV-2. METHODS: Descriptive study of all the psychological/psychiatric symptoms, including anxiety, panic attacks, insomnia, and agitation reported to the Mexican Epidemiological Surveillance System from 21 December 2020 to 27 April 2021, among adult (≥18 years old) recipients of 7,812,845 doses of BNT162b2, ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, or CoronaVac. The factors associated with their development are determined by multivariate regression analysis. RESULTS: There were 19,163 AEFI reports during the study period; amongst them, 191 (1%) patients had psychological/psychiatric symptoms (median age of 41 years, interquartile range of 32-54; 149 [78%] women) for an observed incidence of 2.44 cases per 100,000 administered doses (95% confidence interval [CI] 2.12-2.82), 72.8% of psychiatric AEFIs were reported among recipients of BNT162b2. The median time from vaccination to symptom onset was 35 min (interquartile range: 10-720). Overall, the most common psychological/psychiatric symptoms were anxiety in 129 (67.5%) patients, panic attacks in 30 (15.7%), insomnia in 25 (13%), and agitation in 11 (5.7%). After adjusting for the confounding factors, the odds for developing psychological/psychiatric symptoms were higher for those concurrently reporting syncope (odds ratio [OR]: 4.73, 95% CI: 1.68-13.33); palpitations (OR: 2.47, 95% CI: 1.65-3.70), and dizziness (OR: 1.59, 95% CI: 1.10-2.28). CONCLUSION: In our population, psychological/psychiatric symptoms were extremely infrequent AEFIs. No severe psychiatric AEFIs were reported. Immunization stress-related responses might explain most of the detected cases.

Headache related to personal protective equipment in healthcare workers during COVID-19 pandemic in Mexico: baseline and 6-month follow-up.

BACKGROUND AND AIM: Headaches related to the use of personal protective equipment (PPE) could affect performance at work in healthcare personnel. Our aim was to describe the prevalence and risk factors for headaches related to PPE, in the personnel of a specialized coronavirus disease 2019 (COVID-19) tertiary hospital. METHODS: In this cross-sectional survey study, we invited healthcare workers from COVID-19 referral center in Mexico (May 22-June 19, 2020) to answer a standardized structure questionnaire on characteristics of new-onset PPE-related headache or exacerbation of primary headache disorder. Participants were invited regardless of whether they had a current headache to avoid selection bias. This is the primary analysis of these data. RESULTS: Two hundred and sixty-eight subjects were analyzed, 181/268 (67.5%) women, 177/268 (66%) nurses, mean age 28 years. The prevalence of PPE-related headache was 210/268 (78.4%). Independent risk factors were occupation other than physician (OR 1.59, 95% CI 1.20-2.10), age > 30 years (OR 2.54, 95% CI 1.25-5.14), and female sex (OR 3.58, 95% CI 1.86-6.87). In the 6-month follow-up, 13.1% of subjects evolve to chronic headache, with stress as predictive risk factor. CONCLUSION: The frequency of PPE-associated headache is high, and a subgroup could evolve to chronic headache. More studies are necessary to improve the knowledge about this condition.

Ethnicity and other COVID-19 death risk factors in Mexico.

Introduction: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop coronavirus disease 2019 (COVID-19). Risk factors associated with death vary among countries with different ethnic backgrounds. We aimed to describe the factors associated with death in Mexicans with confirmed COVID-19. Material and methods: We analysed the Mexican Ministry of Health's official database on people tested for SARS-CoV-2 infection by real-time reverse transcriptase-polymerase chain reaction (rtRT-PCR) of nasopharyngeal fluids. Bivariate analyses were performed to select characteristics potentially associated with death, to integrate a Cox-proportional hazards model. Results: As of May 18, 2020, a total of 177,133 persons (90,586 men and 86,551 women) in Mexico received rtRT-PCR testing for SARS-CoV-2. There were 5332 deaths among the 51,633 rtRT-PCR-confirmed cases (10.33%, 95% CI: 10.07-10.59%). The median time (interquartile range, IQR) from symptoms onset to death was 9 days (5-13 days), and from hospital admission to death 4 days (2-8 days). The analysis by age groups revealed that the significant risk of death started gradually at the age of 40 years. Independent death risk factors were obesity, hypertension, male sex, indigenous ethnicity, diabetes, chronic kidney disease, immunosuppression, chronic obstructive pulmonary disease, age > 40 years, and the need for invasive mechanical ventilation (IMV). Only 1959 (3.8%) cases received IMV, of whom 1893 were admitted to the intensive care unit (96.6% of those who received IMV). Conclusions: In Mexico, highly prevalent chronic diseases are risk factors for death among persons with COVID-19. Indigenous ethnicity is a poorly studied factor that needs more investigation.

Delirium and Associated Factors in a Cohort of Hospitalized Patients With Coronavirus Disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic dramatically increased the number of patients requiring treatment in an intensive care unit or invasive mechanical ventilation worldwide. Delirium is a well-known neuropsychiatric complication of patients with acute respiratory diseases, representing the most frequent clinical expression of acute brain dysfunction in critically ill patients, especially in those undergoing invasive mechanical ventilation. Among hospitalized patients with COVID-19, delirium incidence ranges from 11% to 80%, depending on the studied population and hospital setting. OBJECTIVE: To determine risk factors for the development of delirium in hospitalized patients with COVID-19 pneumonia. METHODS: We retrospectively studied consecutive hospitalized adult (≥18 y) patients with confirmed COVID-19 pneumonia from March 15 to July 15, 2020, in a tertiary-care hospital in Mexico City. Delirium was assessed by the attending physician or trained nurse, with either the Confusion Assessment Method for the Intensive Care Unit or the Confusion Assessment Method brief version, according to the appropriate diagnostic tool for each hospital setting. Consultation-liaison psychiatrists and neurologists confirmed all diagnoses. We calculated adjusted hazard ratios (aHR) with 95% confidence interval (CI) using a Cox proportional-hazards regression model. RESULTS: We studied 1017 (64.2% men; median age, 54 y; interquartile range 44-64), of whom 166 (16.3%) developed delirium (hyperactive in 75.3%); 78.9% of our delirium cases were detected in patients under invasive mechanical ventilation. The median of days from admission to diagnosis was 14 (interquartile range 8-21) days. Unadjusted mortality rates between delirium and no delirium groups were similar (23.3% vs. 24.1; risk ratio 0.962, 95% CI 0.70-1.33). Age (aHR 1.02, 95% CI 1.01-1.04; P = 0.006), an initial neutrophil-to-lymphocyte ratio ≥9 (aHR 1.81, 95% CI 1.23-2.65; P = 0.003), and requirement of invasive mechanical ventilation (aHR 3.39, 95% CI 1.47-7.84; P = 0.004) were independent risk factors for in-hospital delirium development. CONCLUSIONS: Delirium is a common in-hospital complication of patients with COVID-19 pneumonia, associated with disease severity; given the extensive number of active COVID-19 cases worldwide, it is essential to detect patients who are most likely to develop delirium during hospitalization. Improving its preventive measures may reduce the risk of the long-term cognitive and functional sequelae associated with this neuropsychiatric complication.

Critical role of acute hypoxemia on the cognitive impairment after severe COVID-19 pneumonia: a multivariate causality model analysis.

BACKGROUND: A high proportion of coronavirus disease 2019 (COVID-19) survivors may develop long-term cognitive impairment. We aimed to develop a multivariate causal model exposing the links between COVID-19-associated biomarkers, illness-related variables, and their effects on cognitive performance. METHODS: In this prospective study, we assess the potential drivers for the development of cognitive impairment in patients with severe COVID-19 pneumonia aged ≥ 18 years at 6-month follow-up after hospital discharge, using the Montreal Cognitive Assessment (MoCA). Patients with pre-existing cognitive impairment were excluded. Laboratory results at hospital admission were clustered by principal component analysis (PCA) and included in a path analysis model evaluating the causal relationship between age, comorbidities, hypoxemia, invasive mechanical ventilation (IMV) requirement, in-hospital delirium, and cognitive performance. RESULTS: We studied 92 patients: 54 (58.7%) men and 38 (41.3%) women, with median age of 50 years (interquartile range 42-55), among whom 50 (54.4%) tested positive for cognitive impairment at 6-month follow-up. Path analysis revealed a direct link between the thrombo-inflammatory component of PCA (C-reactive protein, fibrinogen, and neutrophils) and hypoxemia severity at hospital admission. Our model showed that low PaO2/FiO2 ratio values, unlike the thrombo-inflammatory component, had a direct effect on cognitive performance, independent from age, in-hospital delirium, and invasive mechanical ventilation. CONCLUSION: In this study, biomarkers of thrombo-inflammation in COVID-19 and low PaO2/FiO2 had a negative effect on cognitive performance 6 months after hospital discharge. These results highlight the critical role of hypoxemia as a driver for impaired cognition in the mid-term.

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.

Characteristics and predictors for silent hypoxemia in a cohort of hospitalized COVID-19 patients.

BACKGROUND: An intriguing feature recently unveiled in some COVID-19 patients is the "silent hypoxemia" phenomenon, which refers to the discrepancy of subjective well-being sensation while suffering hypoxia, manifested as the absence of dyspnea. OBJECTIVE: To describe the clinical characteristics and predictors of silent hypoxemia in hospitalized COVID-19 patients. METHODS: We conducted a prospective cohort study including consecutive hospitalized adult (≥ 18 years) patients with confirmed COVID-19 presenting to the emergency department with oxygen saturation (SpO2) ≤ 80% on room air from March 15 to June 30, 2020. We analyzed the characteristics, disease severity, and in-hospital outcomes of patients presenting with dyspnea and those without dyspnea (silent hypoxemia). RESULTS: We studied 470 cases (64.4% men; median age 55 years, interquartile range 46-64). There were 447 (95.1%) patients with dyspnea and 23 (4.9%) with silent hypoxemia. The demographic and clinical characteristics, comorbidities, laboratory and imaging findings, disease severity, and outcomes were similar between groups. Higher breathing and heart rates correlated significantly with lower SpO2 in patients with dyspnea but not in those with silent hypoxemia. Independent predictors of silent hypoxemia were the presence of new-onset headache (OR 2.919, 95% CI 1.101-7.742; P = 0.031) and presenting to the emergency department within the first eight days after symptoms onset (OR 3.183, 95% CI 1.024-9.89; P = 0.045). CONCLUSIONS: Patients with silent hypoxemia sought medical attention earlier and had new-onset headache more often. They were also likely to display lower hemodynamic compensatory responses to hypoxemia, which may underestimate the disease severity.

Levosulpiride Relieved Persistent Hiccups in a Patient With COVID-19 and Vascular Cognitive Impairment.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a systemic illness that implies neurological features and complications. Persistent (>48 hours) hiccups (ie, singultus or hiccoughs) have been recently described as a rare presentation of COVID-19. Even when considered benign, the frequency and duration of hiccup spells can be burdensome and sometimes difficult to treat. CASE PRESENTATION: We report the case of a 62-year-old man known by the treating physicians for vascular cognitive impairment, who consulted for progressive persistent hiccups that commenced 5 days earlier, about 24 hours after testing positive for the severe acute respiratory syndrome coronavirus 2 by real-time reverse transcription polymerase chain reaction. The patient could barely sleep because the hiccups reached the highest rate of 47 per minute in a spell lasting almost 72 hours. The patient initially received levomepromazine 25 mg by mouth, but sedation and delirium impeded the continuation of treatment, which only reduced the frequency of the hiccup spells by about 25%. Afterward, the patient was offered levosulpiride 25 mg thrice a day by mouth, resulting in a steady reduction in the hiccups rate, as well as the duration and daily frequency of spells, which disappeared after 3 days of levosulpiride treatment. COVID-19 pneumonia was moderate by chest computed tomography scan imaging and biomarkers, meriting continuous oxygen therapy, dexamethasone 6 mg once a day by mouth for 10 days, and enoxaparin 40 mg once a day, subcutaneously, for 7 days (due to elevated D-dimer serum concentration). Oxygen therapy was gradually withdrawn after 12 days. CONCLUSIONS: Oral levosulpiride is a suitable option in persistent hiccups that occur in patients with COVID-19 pneumonia. To our knowledge, this is the fourth published case of persistent hiccups as a clinical feature of COVID-19.

Neurologic manifestations in hospitalized patients with COVID-19 in Mexico City.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a systemic entity that frequently implies neurologic features at presentation and complications during the disease course. We aimed to describe the characteristics and predictors for developing in-hospital neurologic manifestations in a large cohort of hospitalized patients with COVID-19 in Mexico City. METHODS: We analyzed records from consecutive adult patients hospitalized from March 15 to June 30, 2020, with moderate to severe COVID-19 confirmed by reverse transcription real-time polymerase chain reaction (rtRT-PCR) for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neurologic syndromes were actively searched by a standardized structured questionnaire and physical examination, confirmed by neuroimaging, neurophysiology of laboratory analyses, as applicable. RESULTS: We studied 1,072 cases (65% men, mean age 53.2±13 years), 71 patients had pre-existing neurologic diseases (diabetic neuropathy: 17, epilepsy: 15, history of ischemic stroke: eight, migraine: six, multiple sclerosis: one, Parkinson disease: one), and 163 (15.2%) developed a new neurologic complication. Headache (41.7%), myalgia (38.5%), dysgeusia (8%), and anosmia (7%) were the most common neurologic symptoms at hospital presentation. Delirium (13.1%), objective limb weakness (5.1%), and delayed recovery of mental status after sedation withdrawal (2.5%), were the most common new neurologic syndromes. Age, headache at presentation, preexisting neurologic disease, invasive mechanical ventilation, and neutrophil/lymphocyte ratio ≥9 were independent predictors of new in-hospital neurologic complications. CONCLUSIONS: Even after excluding initial clinical features and pre-existing comorbidities, new neurologic complications in hospitalized patients with COVID-19 are frequent and can be predicted from clinical information at hospital admission.

Detection of Pulmonary Shunts by Transcranial Doppler in Hospitalized Non-mechanically Ventilated Coronavirus Disease-19 Patients.

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated disease coronavirus disease 2019 (COVID-19), hypoxemia mechanisms differ from those observed in acute respiratory distress syndrome. Hypoxemia and respiratory failure in COVID- 19 are attributed to pulmonary angiopathy, increasing physiological pulmonary shunting1-3.

COVID-19-related diffuse posthypoxic leukoencephalopathy and microbleeds masquerades as acute necrotizing encephalopathy.

BACKGROUND: The complications of coronavirus disease 2019 (COVID-19), the clinical entity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are not limited to the respiratory system. Leukoencephalopathy with microbleeds is increasingly seen in patients with COVID-19. New information is needed to delineate better the clinical implications of this infectious disease. CASE REPORT: A 46-year-old man with confirmed SARS-CoV-2 infection was admitted to the intensive care unit (ICU) with severe COVID-19. After transfer to the general wards, the patient was noted drowsy, disorientated, with slow thinking and speech. A brain MRI showed bilateral symmetrical hyperintense lesions in the deep and subcortical whiter matter, involving the splenium of the corpus callosum, as well as multiple microhemorrhages implicating the splenium and subcortical white matter. No contrast-enhanced lesions were observed in brain CT or MRI. CSF analysis showed no abnormalities, including a negative rtRT-PCR for SARS-CoV-2. An outpatient follow-up visit showed near-complete clinical recovery and resolution of the hyperintense lesions on MRI, without microbleeds change. CONCLUSION: We present the case of a survivor of severe COVID-19 who presented diffuse posthypoxic leukoencephalopathy, and microbleeds masquerading as acute necrotizing encephalopathy. We postulate that this kind of cerebral vasogenic edema with microbleeds could be the consequence of hypoxia, inflammation, the prothrombotic state and medical interventions such as mechanical ventilation and anticoagulation.