Mild and moderate COVID-19 during Alpha, Delta and Omikron pandemic waves in urban Maputo, Mozambique, December 2020-March 2022: a population-based surveillance study (preprint)

In sub-Saharan Africa, reported COVID-19 numbers have been lower than anticipated, even when considering populations younger age. The extent to which risk factors, established in industrialised countries, impact the risk of infection and of disease in populations in sub-Saharan Africa, remains unclear. We estimated the incidence of mild and moderate COVID-19 in urban Mozambique and analysed factors associated with infection and disease in a population-based surveillance study. During December 2020-March 2022, households of a population cohort in Polana Canico, Maputo, Mozambique, were contacted biweekly. Residents reporting any respiratory sign, anosmia, or ageusia, were asked to self-administer a nasal swab, for SARS-CoV-2 PCR testing. Of a subset of 1400 participants, dried blood spots were repeatedly collected three-monthly from finger pricks at home. Antibodies against SARS-CoV-2 spike glycoprotein and nucleocapsid protein were detected using an in-house developed multiplex antibody assay. We estimated the incidence of respiratory illness and COVID-19, and SARS-CoV-2 seroprevalence. We used Cox regression models, adjusting for age and sex, to identify factors associated with first symptomatic COVID-19 and with SARS-CoV-2 sero-conversion in the first six months. During 11925 household visits in 1561 households, covering 6049 participants (median 21 years, 54.8% female, 7.3% disclosed HIV positive), 1895.9 person-years were followed up. Per 1000 person-years, 364.5 (95%CI 352.8-376.1) respiratory illness episodes of which 72.2 (95%CI 60.6-83.9) COVID-19 confirmed, were reported. Of 1412 participants, 2185 blood samples were tested (median 30.6 years, 55.2% female). Sero-prevalence rose from 4.8% (95%CI 1.1-8.6%) in December 2020 to 34.7% (95%CI 20.2-49.3%) in June 2021, when 3.0% were vaccinated. Increasing age (strong gradient in hazard ratio, HR, up to 15.70 in [≥]70 year olds, 95%CI 3.74-65.97), leukaemia, chronic lung disease, hypertension, and overweight increased risk of COVID-19. We found no increased risk of COVID-19 in people with HIV or tuberculosis. Risk of COVID-19 was lower among residents in the lowest socio-economic quintile (HR 0.16, 95%CI 0.04-0.64), with no or limited handwashing facilities, and who shared bedrooms (HR 0.42, 95%CI 0.25-0.72). Older age also increased the risk of SARS-CoV-2 seroconversion (HR 1.57 in 60-69 year olds, 95%CI 1.03-2.39). We found no associations between SARS-CoV-2 infection risk and socio-economic, behavioural factors and comorbidities. Active surveillance in an urban population cohort confirmed frequent COVID-19 underreporting, yet indicated that the large majority of cases were mild and non-febrile. In contrast to industrialised countries, deprivation did not increase the risk of infection nor disease.

Serological surveillance reveals a high exposure to SARS-CoV-2 and altered immune response among COVID-19 unvaccinated Cameroonian individuals (preprint)

Background Surveillance of COVID-19/SARS-CoV-2 dynamics is crucial to understanding natural history and providing insights into the populations exposure risk and specific susceptibilities. This study investigated the seroprevalence of SARS-CoV-2 antibodies, its predictors, and immunological status among unvaccinated patients in Cameroon. Materials and Methods A multicentre cross-sectional study was conducted between January and September 2022 in the town of Douala. Patients were consecutively recruited, and data of interest were collected using a questionnaire. Blood samples were collected to determine Immunoglobin titres (IgM and IgG) by ALFA, CD4+ cells by flow cytometry, and interferon gamma (IFN- {gamma}) and interleukin-6 (IL-6) by ELISA. Results A total of 342 patients aged 41.5 {+/-} 13.9 years were included. Most participants (75.8%) were asymptomatic. The overall prevalence of IgM and IgG was 49.1% and 88.9%, respectively. Ageusia and anosmia have displayed the highest positive predictive values (90.9% and 82.4%) and specificity (98.9% and 98.3%). The predictors of IgM seropositivity were being aged 60 - 70 years (aOR = 0.54, p = 0.02) and ageusia (aOR = 9.31, p = 0.01), whereas those of IgG seropositivity included health facility (aOR = 0.23, p = 0.02) and ageusia (aOR = 0.21, p = 0.04). CD4+, IFN-{gamma}, and IL-6 were impaired in seropositive individuals, with a confounding role of socio-demographic factors or comorbidities. Conclusion Although the WHO declared the end of COVID-19 as a public health emergency, the findings of this study indicate the need for continuous surveillance to adequately control the disease in Cameroon.

Unravelling anosmia, ageusia and clinical presentations in hospitalized Taiwanese patients with COVID-19: Insights and Implications (preprint)

Objectives The objective of this study was to investigate the clinical characteristics and outcomes of hospitalized COVID-19 patients presenting with anosmia and/or ageusia symptoms.Methods We conducted a retrospective observational study among 231 hospitalized patients with COVID-19 in Taiwan from April 2021 to July 2021. Detailed initial clinical symptoms, dyspnea grading, laboratory investigations, and admission outcomes were analyzed to elucidate the significance of anosmia and/or ageusia.Results Cough, fever, and dyspnea were the most common symptoms, while anosmia and/or ageusia accounted for only 8% of symptoms in hospitalized patients. Patients presenting with anosmia and/or ageusia had more severe initial clinical symptoms and comorbidities. A higher proportion of patients with anosmia and/or ageusia underwent initial endotracheal intubation and received emergency monoclonal antibody treatment for COVID-19 than those without these symptoms. However, there were no significant differences in the levels of inflammatory markers between the two groups.Conclusion Our study highlights the distinct clinical presentations of anosmia and/or ageusia in hospitalized COVID-19 patients. Anosmia and/or ageusia could be an important predictor of disease severity and may warrant early intervention in COVID-19 patients. Further studies are needed to confirm these findings

The impact of injury of the chorda tympani nerve during primary stapes surgery or cochlear implantation on taste function, quality of life and food preferences: A study protocol for a double-blind prospective prognostic association study.

BACKGROUND: The chorda tympani nerve (CTN) is a mixed nerve, which carries sensory and parasympathetic fibres. The sensory component supplies the taste sensation of the anterior two-thirds of the ipsilateral side of the tongue. During middle ear surgery the CTN is exposed and frequently stretched or sacrificed, because it lacks a bony covering as it passes through the middle ear. Injury may cause hypogeusia, ageusia or altered taste sensation of the ipsilateral side of the tongue. To date, there is no consensus regarding which type of CTN injury (sacrificing or stretching), during middle ear surgery, leads to the least burden for the patient. METHODS: A double-blind prospective prognostic association study was designed in a single medical centre in the Netherlands to determine the effect of CTN injury on postoperative taste disturbance and quality of life. 154 patients, who will undergo primary stapes surgery or cochlear implantation will be included. The taste sensation, food preferences and quality of life of these patients will be evaluated preoperatively and at one week, six weeks and six months postoperatively using the Taste Strip Test, Electrogustometry, supplementary questionnaire on taste disturbance, Macronutrient and Taste Preference Ranking Task, Appetite, Hunger and Sensory Perception questionnaire and Questionnaire of Olfactory Disorders to assess the association of these outcomes with CTN injury. Evaluation of olfactory function will only take place preoperatively and at one week postoperatively using the Sniffin' Sticks. The patient and outcome assessor are blinded to the presence or absence of CTN injury. DISCUSSION: This study is the first to validate and quantify the effect of chorda tympani nerve injury on taste function. The findings of this study may lead to evidence-based proof of the effect of chorda tympani injury on taste function with consequences for surgical strategies. TRIAL REGISTRATION: Netherlands Trial Register NL9791. Registered on 10 October 2021.

Diode laser in management of loss of taste sensation in patients with post-COVID syndrome: a randomized clinical trial.

OBJECTIVE: Loss of taste (ageusia) is a symptom observed following recovery from COVID-19 infection. The loss of taste and smell sensation may negatively affect patients' quality of life (QoL). The present study aimed to evaluate the effectiveness of the Diode Laser in managing loss of taste sensation in patients with post-COVID syndrome versus the placebo. MATERIAL AND METHOD: The study sample was 36 patients who complained of persistent loss of taste sensation following COVID-19. The patients were randomly assigned to one of the two groups according to the received treatment: Group I (laser treatment) and Group II (light treatment), with each patient receiving a diode laser treatment or placebo from the same operator. Taste sensation was subjectively measured after treatment for four weeks. RESULTS: The results demonstrated a significant difference between both groups regarding taste restoration after one month (p = 0.041), with Group II having a significantly higher percentage of cases 7 (38.9%) with partial taste restoration. In contrast, a significantly higher proportion of Group I 17 cases (94.4%) had complete taste restoration (p < 0.001). CONCLUSION: The present study concluded that using a Diode laser 810 nm aided in a more rapid recovery from loss of taste dysfunction.

Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic.

BACKGROUND: Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations. METHODS: PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes. CONCLUSION: Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality.

Les impacts neurologiques et neuropsychiatriques d'une infection à la COVID-19. CONTEXTE: Bien qu'il s'agisse principalement d'une maladie des voies respiratoires, la maladie infectieuse à coronavirus apparue en 2019 (COVID-19) s'est avérée avoir un lien de causalité avec une pléthore d'impacts d'ordre neurologique, neuropsychiatrique et psychologique. Cette étude entend donc analyser ces impacts tout en discutant l'évolution des recommandations thérapeutiques se rapportant à cette maladie. MÉTHODES: Les bases de données PubMed et Google Scholar ont été interrogées entre les 1er janvier et 30 mai 2020. Les termes clés suivants ont été utilisés : « COVID-19 ¼, « SRAS ­ CoV-2 ¼, « Pandémie ¼, « Neuro ­ COVID ¼, « AVC ­ COVID ¼, « Épilepsie ­ COVID ¼, « COVID ­ encéphalopathie ¼, « SRAS ­ CoV-2 ­ encéphalite ¼, « SRAS ­ CoV-2 ­ rhabdomyolyse ¼, « COVID ­ maladie démyélinisante ¼, « Manifestations neurologiques ¼, « Manifestations psychosociales ¼, « Recommandations thérapeutiques ¼, « COVID-19 et changement thérapeutiques ¼, « Psychiatrie ¼, « Marginalisés ¼, « Télémédecine ¼, « Santé mentale ¼, « Quarantaine ¼, « Infodémique ¼ et « Médias sociaux ¼. De plus, quelques articles de journaux relatifs à la pandémie de COVID-19 et à ses impacts psychosociaux ont également été ajoutés en fonction du contexte. RÉSULTATS: Il appert que les manifestations neurologiques et neuropsychiatriques des infections à la COVID-19 sont nombreuses. Les caractéristiques cliniques d'une implication des systèmes nerveux central et périphérique sautent désormais aux yeux. Ces caractéristiques ont fait l'objet d'une brève analyse systématique à l'aide de publications scientifiques. En outre, la plupart des impacts d'ordre psychologique de cette pandémie se sont révélés moins apparents que les changements réglementaires, socioéconomiques et psychosociaux. CONCLUSION: Les manifestations neurologiques et neuropsychiatriques de cette maladie ne font que commencer à être élucidées. Cela exige donc une capacité accrue de vigilance en vue d'un diagnostic rapide, et ce, afin de prévenir des complications additionnelles et une mortalité accrue.

Solitary Anosmia/Ageusia in Prison: Results From a COVID-19 Cluster.

A prison setting with its congregate environment is at high risk for widespread transmission of respiratory illnesses. Identifying COVID-19 cases as early as possible and isolating cases and tracing contacts is critical to halting the spread of this disease. The Centers for Disease Control and Prevention (CDC) added new loss of taste or smell to its list of symptoms and, initially, only if associated with at least one of six other symptoms. The CDC has since updated the guidance to remove this qualifier as of May 13, 2020. New loss of taste or smell, alone, can help to identify COVID-19 cases. Solitary anosmia/ageusia should be strongly considered in routine symptom screening protocols for COVID-19.

Post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors: A systematic review and meta-analysis.

Background: Post-acute coronavirus disease 2019 (COVID-19) symptoms occurred in most of the COVID-19 survivors. However, few studies have examined the issue of whether hospitalization results in different post-acute COVID-19 symptom risks. This study aimed to compare potential COVID-19 long-term effects in hospitalized and non-hospitalized COVID-19 survivors. Methods: This study is designed as a systematic review and meta-analysis of observational studies. A systematic search of six databases was performed for identifying articles published from inception until April 20th, 2022, which compared post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors using a predesigned search strategy included terms for SARS-CoV-2 (eg, COVID, coronavirus, and 2019-nCoV), post-acute COVID-19 Syndrome (eg, post-COVID, post COVID conditions, chronic COVID symptom, long COVID, long COVID symptom, long-haul COVID, COVID sequelae, convalescence, and persistent COVID symptom), and hospitalization (hospitalized, in hospital, and home-isolated). The present meta-analysis was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement using R software 4.1.3 to create forest plots. Q statistics and the I 2 index were used to evaluate heterogeneity in this meta-analysis. Results: Six observational studies conducted in Spain, Austria, Switzerland, Canada, and the USA involving 419 hospitalized and 742 non-hospitalized COVID-19 survivors were included. The number of COVID-19 survivors in included studies ranged from 63 to 431, and follow-up data were collected through visits in four studies and another two used an electronic questionnaire, visit and telephone, respectively. Significant increase in the risks of long dyspnea (OR = 3.18, 95% CI = 1.90-5.32), anxiety (OR = 3.09, 95% CI = 1.47-6.47), myalgia (OR = 2.33, 95% CI = 1.02-5.33), and hair loss (OR = 2.76, 95% CI = 1.07-7.12) risk were found in hospitalized COVID-19 survivors compared with outpatients. Conversely, persisting ageusia risk was significantly reduced in hospitalized COVID-19 survivors than in non-hospitalized patients. Conclusion: The findings suggested that special attention and patient-centered rehabilitation service based on a needs survey should be provided for hospitalized COVID-19 survivors who experienced high post-acute COVID-19 symptoms risk.

Neurological and Psychiatric Manifestations of Post-COVID-19 Conditions.

BACKGROUND: We aimed to investigate the factors associated with neurological manifestations of post-coronavirus disease 2019 (COVID-19) conditions. METHODS: We retrospectively collected data from 440 patients who visited our post-COVID-19 clinic more than 4 weeks after severe acute respiratory syndrome coronavirus 2 infection. We analyzed the prevalence of different neurological symptoms (brain fog, memory impairment, headache, and dizziness) and assessed the associated factors. RESULTS: Brain fog was the most common symptom, observed in 170 patients (38.6%), followed by headaches (n = 137, 31.1%), dizziness (n = 128, 29%), and memory impairment (n = 104, 23.6%). Brain fog was associated with hyposmia or hypogeusia (odds ratio [OR], 2.54; P < 0.001), Fatigue Severity Scale (FSS) (OR, 1.06; P < 0.001), and Hospital Anxiety and Depression Scale-Anxiety (OR, 1.09; P = 0.037). Memory impairment was associated with sleep problems (OR, 2.83; P < 0.001), FSS (OR, 1.05; P < 0.001), and age (OR, 1.02; P = 0.015). Headache was associated with sleep problems (OR, 2.28; P = 0.001), sex (OR, 1.68; P = 0.042), and FSS (OR, 1.04; P < 0.001). Dizziness was associated with sleep problems (OR, 2.88; P < 0.001), and FSS (OR, 1.04; P < 0.001). The incidence of brain fog (P < 0.001), memory impairment (P < 0.001), dizziness (P = 0.007), and headache (P = 0.045) accompanied by hyposmia and hypogeusia was higher in patients with the aforementioned symptoms than in those without. CONCLUSION: This study suggests that there is a relationship between neurological symptoms and other clinical factors, such as fatigue, depression, anxiety, hyposmia, and hypogeusia.

Oral health related quality of life and the prevalence of ageusia and xerostomia in active and recovered COVID-19 Patients.

Background: Salivary disturbance is associated with patients who either have an active coronavirus disease 2019 (COVID-19) or have recovered from coronavirus infection along with loss of taste sensation. In addition, COVID-19 infection can drastically compromise quality of life of individuals. Objective: This study aimed to analyze xerostomia, ageusia and the oral health impact in coronavirus disease-19 patients utilizing the Xerostomia Inventory scale-(XI) and the Oral Health Impact Profile-14. Methods: In this cross-sectional survey-based study, data was collected from 301 patients who suffered and recovered from COVID-19. Using Google Forms, a questionnaire was developed and circulated amongst those who were infected and recovered from coronavirus infection. The Xerostomia Inventory (XI) and Oral Health Impact Profile-14 were used to assess the degree and quality of life. A paired T-test and Chi-square test were used to analyze the effect on xerostomia inventory scale-(XI) and OHIP-14 scale scores. A p-value of 0.05 was considered as statistically significant. Results: Among 301 participants, 54.8% were females. The prevalence of xerostomia in participants with active COVID-19 disease was 39.53% and after recovery 34.88%. The total OHIP-14 scores for patients in the active phase of infection was 12.09, while 12.68 in recovered patients. A significant difference was found between the mean scores of the xerostomia inventory scale-11 and OHIP-14 in active and recovered COVID patients. Conclusion: A higher prevalence of xerostomia was found in COVID-19 infected patients (39.53%) compared to recovered patients (34.88%). In addition, more than 70% reported aguesia. COVID-19 had a significantly higher compromising impact on oral function of active infected patients compared to recovered patients.

Can photobiomodulation restore anosmia and ageusia induced by COVID-19? A pilot clinical study.

Along with other COVID-19 clinical manifestations, management of both olfactory and gustatory dysfunction have drawn a considerable attention. Photobiomodulation (PBM) has emerged to be a possible effective therapy in restoring taste and smell functionality, but the evidence is scarce. Hence, the present pilot study is aimed to evaluate the effectiveness of intranasal and intraoral PBM administrations in management of anosmia and ageusia respectively. Twenty Caucasian subjects who diagnosed with anosmia and ageusia were recruited. Visual analogue scale was utilised to evaluate patients' self-reported for both olfactory and gustatory functionality. The laser-PBM parameters and treatment protocols for anosmia and ageusia were as follows respectively: 660 nm, 100 mW, two points intranasally, 60 J/session, 12 sessions; dual wavelengths (660 nm and 808 nm), 100 mW, three points intraorally, 216 J/session, 12 sessions. Our results showed a significant functionality improvement of both olfactory and gustatory functionality. Extensive studies with large data and long-term follow-up period are warranted.

Neurological symptoms and comorbidity profile of hospitalized patients with COVID-19.

BACKGROUND: The neurological manifestations in COVID-19 adversely impact acute illness and post-disease quality of life. Limited data exist regarding the association of neurological symptoms and comorbid individuals. OBJECTIVE: To assess neurological symptoms in hospitalized patients with acute COVID-19 and multicomorbidities. METHODS: Between June 2020 and July 2020, inpatients aged 18 or older, with laboratory-confirmed COVID-19, admitted to the Hospital São Paulo (Federal University of São Paulo), a tertiary referral center for high complexity cases, were questioned about neurological symptoms. The Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire was used. The data were analyzed as a whole and whether subjective olfactory dysfunction was present or not. RESULTS: The mean age of the sample was 55 ± 15.12 years, and 58 patients were male. The neurological symptoms were mostly xerostomia (71%), ageusia/hypogeusia (50%), orthostatic intolerance (49%), anosmia/hyposmia (44%), myalgia (31%), dizziness (24%), xerophthalmia (20%), impaired consciousness (18%), and headache (16%). Furthermore, 91% of the patients had a premorbidity. The 44 patients with subjective olfactory dysfunction were more likely to have hypertension, diabetes, weakness, shortness of breath, ageusia/hypogeusia, dizziness, orthostatic intolerance, and xerophthalmia. The COMPASS-31 score was higher than that of previously published controls (14.85 ± 12.06 vs. 8.9 ± 8.7). The frequency of orthostatic intolerance was 49% in sample and 63.6% in those with subjective olfactory dysfunction (2.9-fold higher risk compared to those without). CONCLUSION: A total of 80% of inpatients with multimorbidity and acute COVID-19 had neurological symptoms. Chemical sense and autonomic symptoms stood out. Orthostatic intolerance occurred in around two-thirds of the patients with anosmia/hyposmia. Hypertension and diabetes were common, mainly in those with anosmia/hyposmia.

ANTECEDENTES: As manifestações neurológicas na COVID-19 impactam adversamente na enfermidade aguda e na qualidade de vida após a doença. Dados limitados existem em relação a associação de sintomas neurológicos e indivíduos com comorbidades. OBJETIVO: Avaliar os sintomas neurológicos em pacientes de hospitalizados com COVID-19 aguda e múltiplas comorbidades. MéTODOS: Entre junho e julho de 2020, pacientes de hospitais com idade 18 anos ou acima e COVID-19 laboratorialmente confirmada, admitidos no Hospital São Paulo (Universidade Federal de São Paulo), um centro de referência terciário para casos de alta complexidade, foram perguntados sobre sintomas neurológicos. O questionário Pontuação composta de sintoma autonômico (COMPASS-31) foi usado. Os dados foram analisados no geral e se a disfunção olfatória subjetiva estava presente ou não. RESULTADOS: A média de idade da amostra foi 55 ± 15.12 anos. 58 pacientes eram homens. Os sintomas neurológicos foram principalmente xerostomia (71%), ageusia/hipogeusia (50%), intolerância ortostática (49%), anosmia/hiposmia (44%), mialgia (31%), tontura (24%), xeroftalmia (20%), comprometimento na consciência (18%) e cefaleia (16%). Além disso, 91% dos pacientes tinham uma pré-morbidade. Os 44 pacientes com disfunção olfatória tinham maior chance de ter hipertensão, diabetes, fraqueza, falta de ar, ageusia/hipogeusia, tontura, intolerância ortostática e xeroftalmia. A pontuação do COMPASS-31 foi maior do que a de controles previamente publicados (14,85 ± 12,06 vs. 8,9 ± 8,7). A frequência de intolerância ortostática foi 49% na amostra e 63,6% naqueles com disfunção olfatória subjetiva (risco 2.9 vezes maior comparado com os sem). CONCLUSãO: Um total de 80% dos pacientes hospitalizados com múltiplas morbidades e COVID-19 aguda tinham sintomas neurológicos. Os sintomas do sentido químico e autonômicos se destacaram. A intolerância ortostática ocorreu em cerca de dois terços dos pacientes com anosmia/hiposmia. A hipertensão e o diabetes foram comuns, principalmente naqueles com anosmia/hiposmia.

Neuropsychiatric symptoms in post-COVID-19 long haulers.

BACKGROUND: Long haulers have been recently reported after contracting coronavirus disease (COVID-19). In the present study, we aimed to screen for the neuropsychiatric signs detected <1 to >6 months after infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to determine whether vaccination has an effect on them. METHODS: An online survey was conducted among participants who had been diagnosed with laboratory-confirmed SARS-CoV-2 infection. The clinical signs and durations of neuropsychiatric complaints and their correlations to sex, age, severity of COVID-19 signs, and vaccination status were screened. RESULTS: A total of 2218 individuals, including 1358 females and 860 males, with an age range of 12-70 years, submitted their responses. The respondents experienced cognitive dysfunction, mood alteration, depression, tinnitus, sleep disorders, and loss of taste and smell, with prevalence rates ranging from 18.9% (tinnitus) to 63.9% (loss of taste and smell). Of the respondents, 2.2-7.7% confirmed the persistence of symptoms for >6 months. Tinnitus was the least common complaint, and only 2.2% of the study participants had tinnitus for >6 months. Meanwhile, mood alteration persisted for >6 months in 7.6% of the study participants. More respondents who received two doses of BNT162b2 vaccine showed persistent symptoms than those in the other groups. Disease severity and female sex were identified as potential determinants of the development and persistency of such symptoms. CONCLUSION: Post-COVID neuropsychiatric symptoms were present in considerable percentages of the study participants with SARS-CoV-2 infection, persisting for >6 months in up to 7.6% of the participants.

Long-Term Consequences of Asymptomatic SARS-CoV-2 Infection: A Systematic Review and Meta-Analysis.

Little is known about the long-term consequences of asymptomatic infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to review the data available to explore the long-term consequences of asymptomatic SARS-CoV-2 infection in the real world. We searched observational cohort studies that described the long-term health effects of asymptomatic SARS-CoV-2 infections. Random-effects inverse-variance models were used to evaluate the pooled prevalence (PP) and its 95% confidence interval (CI) of long-term symptoms. Random effects were used to estimate the pooled odds ratios (OR) and its 95%CI of different long-term symptoms between symptomatic and asymptomatic infections. Five studies involving a total of 1643 cases, including 597 cases of asymptomatic and 1043 cases of symptomatic SARS-CoV-2 infection were included in this meta-analysis. The PPs of long-term consequences after asymptomatic SARS-CoV-2 infections were 17.13% (95%CI, 7.55−26.71%) for at least one symptom, 15.09% (95%CI, 5.46−24.73%) for loss of taste, 14.14% (95%CI, −1.32−29.61%) for loss of smell, and 9.33% (95%CI, 3.07−15.60) for fatigue. Compared with symptomatic SARS-CoV-2 infection, asymptomatic infection was associated with a significantly lower risk of developing COVID-19-related sequelae (p < 0.05), with 80% lower risk of developing at least one symptom (OR = 0.20, 95%CI, 0.09−0.45), 81% lower risk of fatigue (OR = 0.19, 95%CI, 0.08−0.49), 90% lower risk of loss of taste/smell (OR = 0.10, 95%CI, 0.02−0.58). Our results suggested that there were long-term effects of asymptomatic SARS-CoV-2 infection, such as loss of taste or smell, fatigue, cough and so on. However, the risk of developing long-term symptoms in asymptomatic SARS-CoV-2 infected persons was significantly lower than those in symptomatic SARS-CoV-2 infection cases.

Coronavirus infection in chemosensory cells.

Clinical manifestations of human coronavirus (HCoV)-related diseases are mostly related to the respiratory system, although secondary complications such as headache, anosmia, ageusia, and myalgia have been reported. HCoV infection and replication in chemosensory cells associated with ageusia and anosmia is poorly understood. Here, we characterized HCoV-OC43 and SARS-CoV-2 infection in two types of chemosensory cells, olfactory and taste cells, with their unique molecular and histological characteristics. We first assessed HCoV-OC43 infection in in vitro cultured human olfactory epithelial cells (hOECs) and fungiform taste papilla (HBO) cells. Interestingly, while both cell types were susceptible to HCoV-OC43 infection, viral replication rates were significantly reduced in HBO cells compared to hOECs. More interestingly, while culture media from hOECs was able to produce secondary infection in Vero cells, there was very limited secondary infection from HBO cells, suggesting that HBO cells may not be able to release infectious virus. On the other hand, unlike HCoV-OC43, SARS-CoV-2 showed comparable levels of viral infection rates in both hOECs and HBO cells. Furthermore, our RT-qPCR-based gene array studies revealed that several key genes involved in taste and olfactory functions were significantly altered by SARS-CoV-2 infection. These results may suggest a possible mechanism associated with chemosensory symptoms, such as anosmia and ageusia in patients infected with SARS-CoV-2.

The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID - results from the prospective population-based COVI-GAPP study (preprint)

Background: During and after mild (no hospitalization) or moderate (hospitalization without ICU) SARS-CoV-2 infections, a wide range of symptoms, including neurological disorders have been reported. It is, however, unknown if these neurological symptoms are associated with brain injury and whether brain injury and related symptoms also emerge in patients suffering from Long-COVID. Neuronal biomarkers such as serum neurofilament light chain and glial fibrillary acidic protein can be used to elucidate neuro-axonal and astroglial injuries. We therefore investigated whether these biomarkers are associated with the COVID-19 infection status (mild-to-moderate), the associated symptoms and Long-COVID. Methods: From 146 individuals of the general population with a post-acute, mild-to-moderate SARS-CoV-2 infection, serum neurofilament light chain (sNfL; marker of intra-axonal neuronal injury) and serum glial fibrillary acidic protein (sGFAP; marker of astrocytic activation/injury) were measured. Samples were taken before, during and after (five and ten months) a SARS-CoV-2 infection. Individual symptoms and Long-COVID status were assessed using questionnaires. Results: Neurological symptoms were described for individuals after a mild and moderate COVID-19 infection, however, serum markers of brain injury (sNfL/sGFAP) did not change after an infection (sNfL: P = 0.74; sGFAP: P = 0.24) and were not associated with headache (P = 0.51), fatigue (P = 0.93), anosmia (P = 0.77) and ageusia (P = 0.47). In participants with Long-COVID, sGFAP (P = 0.038), but not sNfL (P = 0.58) significantly increased but was not associated with neurological symptoms. Conclusion: Neurological symptoms in individuals after a mild-to-moderate SARS-CoV-2 infection with and without Long-COVID were not associated with brain injury, although there was some astroglial injury observed in Long-COVID patients. Funding: The COVI-GAPP study received grants from the Innovative Medicines Initiative (IMI grant agreement number 101005177), the Princely House of Liechtenstein, the government of the Principality of Liechtenstein, and the Hanela Foundation (Switzerland). None of the funders played a role in the study design, data collection, data analysis, data interpretation, writing of the report, or decision to publish.

Momentary gustative-olfactory sensitivity and tonic heart rate variability are independently associated with motivational behavior.

Deficits in motivational functioning including impairments in reward learning or reward sensitivity are common in psychiatric disorders characterized by anhedonia. Recently, anhedonic symptoms have been exacerbated by the pandemic caused by the Coronavirus disease 2019 (COVID-19) in the general population. The present study examined the putative associations between loss of smell (anosmia) and taste (ageusia) sensitivity, irrespective of COVID-19 infection, and anhedonia, measured by a signal-detection task probing the ability to modify behavior as a function of rewards (Probabilistic Reward Task; PRT). Tonic heart rate variability (HRV) was included in the model, due to its association with both smell and taste sensitivity as well as motivational functioning. The sample included 114 healthy individuals (81 females; mean age 22.2 years), who underwent a laboratory session in which dispositional traits, resting HRV and PRT performance were assessed, followed by a 4-days ecological momentary assessment to obtain daily measures of anosmia and ageusia. Lower levels of tonic HRV and lower momentary levels of smell and taste sensitivity were associated with impaired reward responsiveness and ability to shape future behavioral choices based on prior reinforcement experiences. Overall, the current results provide initial correlational evidence that could be fruitfully used to inform future experimental investigations aimed at elucidating the disruptive worldwide mental health consequences triggered by the pandemic.

Anosmia, ageusia, and other COVID-19-like symptoms in association with a positive SARS-CoV-2 test, across six national digital surveillance platforms: an observational study.

BACKGROUND: Multiple voluntary surveillance platforms were developed across the world in response to the COVID-19 pandemic, providing a real-time understanding of population-based COVID-19 epidemiology. During this time, testing criteria broadened and health-care policies matured. We aimed to test whether there were consistent associations of symptoms with SARS-CoV-2 test status across three surveillance platforms in three countries (two platforms per country), during periods of testing and policy changes. METHODS: For this observational study, we used data of observations from three volunteer COVID-19 digital surveillance platforms (Carnegie Mellon University and University of Maryland Facebook COVID-19 Symptom Survey, ZOE COVID Symptom Study app, and the Corona Israel study) targeting communities in three countries (Israel, the UK, and the USA; two platforms per country). The study population included adult respondents (age 18-100 years at baseline) who were not health-care workers. We did logistic regression of self-reported symptoms on self-reported SARS-CoV-2 test status (positive or negative), adjusted for age and sex, in each of the study cohorts. We compared odds ratios (ORs) across platforms and countries, and we did meta-analyses assuming a random effects model. We also evaluated testing policy changes, COVID-19 incidence, and time scales of duration of symptoms and symptom-to-test time. FINDINGS: Between April 1 and July 31, 2020, 514 459 tests from over 10 million respondents were recorded in the six surveillance platform datasets. Anosmia-ageusia was the strongest, most consistent symptom associated with a positive COVID-19 test (robust aggregated rank one, meta-analysed random effects OR 16·96, 95% CI 13·13-21·92). Fever (rank two, 6·45, 4·25-9·81), shortness of breath (rank three, 4·69, 3·14-7·01), and cough (rank four, 4·29, 3·13-5·88) were also highly associated with test positivity. The association of symptoms with test status varied by duration of illness, timing of the test, and broader test criteria, as well as over time, by country, and by platform. INTERPRETATION: The strong association of anosmia-ageusia with self-reported positive SARS-CoV-2 test was consistently observed, supporting its validity as a reliable COVID-19 signal, regardless of the participatory surveillance platform, country, phase of illness, or testing policy. These findings show that associations between COVID-19 symptoms and test positivity ranked similarly in a wide range of scenarios. Anosmia, fever, and respiratory symptoms consistently had the strongest effect estimates and were the most appropriate empirical signals for symptom-based public health surveillance in areas with insufficient testing or benchmarking capacity. Collaborative syndromic surveillance could enhance real-time epidemiological investigations and public health utility globally. FUNDING: National Institutes of Health, National Institute for Health Research, Alzheimer's Society, Wellcome Trust, and Massachusetts Consortium on Pathogen Readiness.

Applying fuzzy qualitative comparative analysis to identify typical symptoms of COVID-19 infection in a primary care unit, Rio de Janeiro, Brazil.

This study aims to identify a set of symptoms that could be predictive of SARS-CoV-2 cases in the triage of Primary Care services with the contribution of Qualitative Comparative Analysis (QCA) using Fuzzy Sets (fsQCA). A cross-sectional study was carried out in a Primary Health Care Unit/FIOCRUZ from 09/17/2020 to 05/05/2021. The study population was suspect cases that performed diagnostic tests for COVID-19. We collected information about the symptoms to identify which configurations are associated with positive and negative cases. For analysis, we used fsQCA to explain the outcomes "being a positive case" and "not being a positive case". The solution term "loss of taste or smell and no headache" showed the highest degree of association with the positive result (consistency = 0.81). The solution term "absence of loss of taste or smell combined with the absence of fever" showed the highest degree of association (consistency = 0,79) and is the one that proportionally best explains the negative result. Our results may be useful to the presumptive clinical diagnosis of COVID-19 in scenarios where access to diagnostic tests is not available. We used an innovative method used in complex problems in Public Health, the fsQCA.