Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19.

BACKGROUND: COVID-19 illness is highly variable, ranging from infection with no symptoms through to pneumonia and life-threatening consequences. Symptoms such as fever, cough, or loss of sense of smell (anosmia) or taste (ageusia), can help flag early on if the disease is present. Such information could be used either to rule out COVID-19 disease, or to identify people who need to go for COVID-19 diagnostic tests. This is the second update of this review, which was first published in 2020. OBJECTIVES: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19. SEARCH METHODS: We undertook electronic searches up to 10 June 2021 in the University of Bern living search database. In addition, we checked repositories of COVID-19 publications. We used artificial intelligence text analysis to conduct an initial classification of documents. We did not apply any language restrictions. SELECTION CRITERIA: Studies were eligible if they included people with clinically suspected COVID-19, or recruited known cases with COVID-19 and also controls without COVID-19 from a single-gate cohort. Studies were eligible when they recruited people presenting to primary care or hospital outpatient settings. Studies that included people who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected all studies, at both title and abstract, and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and assessed risk of bias using the QUADAS-2 checklist, and resolved disagreements by discussion with a third review author. Analyses were restricted to prospective studies only. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic (ROC) space and in dumbbell plots. We estimated summary parameters using a bivariate random-effects meta-analysis whenever five or more primary prospective studies were available, and whenever heterogeneity across studies was deemed acceptable. MAIN RESULTS: We identified 90 studies; for this update we focused on the results of 42 prospective studies with 52,608 participants. Prevalence of COVID-19 disease varied from 3.7% to 60.6% with a median of 27.4%. Thirty-five studies were set in emergency departments or outpatient test centres (46,878 participants), three in primary care settings (1230 participants), two in a mixed population of in- and outpatients in a paediatric hospital setting (493 participants), and two overlapping studies in nursing homes (4007 participants). The studies did not clearly distinguish mild COVID-19 disease from COVID-19 pneumonia, so we present the results for both conditions together. Twelve studies had a high risk of bias for selection of participants because they used a high level of preselection to decide whether reverse transcription polymerase chain reaction (RT-PCR) testing was needed, or because they enrolled a non-consecutive sample, or because they excluded individuals while they were part of the study base. We rated 36 of the 42 studies as high risk of bias for the index tests because there was little or no detail on how, by whom and when, the symptoms were measured. For most studies, eligibility for testing was dependent on the local case definition and testing criteria that were in effect at the time of the study, meaning most people who were included in studies had already been referred to health services based on the symptoms that we are evaluating in this review. The applicability of the results of this review iteration improved in comparison with the previous reviews. This version has more studies of people presenting to ambulatory settings, which is where the majority of assessments for COVID-19 take place. Only three studies presented any data on children separately, and only one focused specifically on older adults. We found data on 96 symptoms or combinations of signs and symptoms. Evidence on individual signs as diagnostic tests was rarely reported, so this review reports mainly on the diagnostic value of symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. RT-PCR was the most often used reference standard (40/42 studies). Only cough (11 studies) had a summary sensitivity above 50% (62.4%, 95% CI 50.6% to 72.9%)); its specificity was low (45.4%, 95% CI 33.5% to 57.9%)). Presence of fever had a sensitivity of 37.6% (95% CI 23.4% to 54.3%) and a specificity of 75.2% (95% CI 56.3% to 87.8%). The summary positive likelihood ratio of cough was 1.14 (95% CI 1.04 to 1.25) and that of fever 1.52 (95% CI 1.10 to 2.10). Sore throat had a summary positive likelihood ratio of 0.814 (95% CI 0.714 to 0.929), which means that its presence increases the probability of having an infectious disease other than COVID-19. Dyspnoea (12 studies) and fatigue (8 studies) had a sensitivity of 23.3% (95% CI 16.4% to 31.9%) and 40.2% (95% CI 19.4% to 65.1%) respectively. Their specificity was 75.7% (95% CI 65.2% to 83.9%) and 73.6% (95% CI 48.4% to 89.3%). The summary positive likelihood ratio of dyspnoea was 0.96 (95% CI 0.83 to 1.11) and that of fatigue 1.52 (95% CI 1.21 to 1.91), which means that the presence of fatigue slightly increases the probability of having COVID-19. Anosmia alone (7 studies), ageusia alone (5 studies), and anosmia or ageusia (6 studies) had summary sensitivities below 50% but summary specificities over 90%. Anosmia had a summary sensitivity of 26.4% (95% CI 13.8% to 44.6%) and a specificity of 94.2% (95% CI 90.6% to 96.5%). Ageusia had a summary sensitivity of 23.2% (95% CI 10.6% to 43.3%) and a specificity of 92.6% (95% CI 83.1% to 97.0%). Anosmia or ageusia had a summary sensitivity of 39.2% (95% CI 26.5% to 53.6%) and a specificity of 92.1% (95% CI 84.5% to 96.2%). The summary positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.55 (95% CI 3.46 to 5.97) and 4.99 (95% CI 3.22 to 7.75) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The summary positive likelihood ratio of ageusia alone was 3.14 (95% CI 1.79 to 5.51). Twenty-four studies assessed combinations of different signs and symptoms, mostly combining olfactory symptoms. By combining symptoms with other information such as contact or travel history, age, gender, and a local recent case detection rate, some multivariable prediction scores reached a sensitivity as high as 90%. AUTHORS' CONCLUSIONS: Most individual symptoms included in this review have poor diagnostic accuracy. Neither absence nor presence of symptoms are accurate enough to rule in or rule out the disease. The presence of anosmia or ageusia may be useful as a red flag for the presence of COVID-19. The presence of cough also supports further testing. There is currently no evidence to support further testing with PCR in any individuals presenting only with upper respiratory symptoms such as sore throat, coryza or rhinorrhoea. Combinations of symptoms with other readily available information such as contact or travel history, or the local recent case detection rate may prove more useful and should be further investigated in an unselected population presenting to primary care or hospital outpatient settings. The diagnostic accuracy of symptoms for COVID-19 is moderate to low and any testing strategy using symptoms as selection mechanism will result in both large numbers of missed cases and large numbers of people requiring testing. Which one of these is minimised, is determined by the goal of COVID-19 testing strategies, that is, controlling the epidemic by isolating every possible case versus identifying those with clinically important disease so that they can be monitored or treated to optimise their prognosis. The former will require a testing strategy that uses very few symptoms as entry criterion for testing, the latter could focus on more specific symptoms such as fever and anosmia.

Therapeutic supplementation with zinc in the management of COVID-19-related diarrhea and ageusia/dysgeusia: mechanisms and clues for a personalized dosage regimen.

Zinc supplementation is indicated for diarrhea and taste disorders, which are both features of COVID-19 . Nevertheless, this strategy has not been tested for the treatment of these secondary complications in the current pandemic. Through an updated review, a practical appraisal was considered as a means of providing a medical nexus of therapeutic zinc regimens as an adjunct in the management of COVID-19-related diarrhea and ageusia/dysgeusia. While diarrhea and taste disorders are consequences of COVID-19, zinc supplementation is useful for non-COVID-19 patients with these clinical problems. The overwhelming evidence for supplementing with zinc in diarrhea and pneumonia is associated with the treatment of children, while for taste disorders the use of supplementing with zinc is more examined in adults. Whereas COVID-19 is more prevalent in adults, precautions should be exercised not to translate the zinc dosage used for children with diarrhea and taste disorders into the current pandemic. Therapeutic doses of zinc used for adults (∼50-150 mg/day of elemental zinc) could be included in the treatment strategies for COVID-19, but this proposal should be examined through randomized studies.

Simultaneously complete but not partial taste and smell losses were associated with SARS-CoV-2 infection.

OBJECTIVES: The aim of this study was to investigate the association between taste and smell losses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and to elucidate whether taste preference influences such taste loss. METHODS: A matched case-control study was conducted in 366 Thai participants, including 122 who were confirmed SARS-CoV-2-positive by RT-PCR (case group) and 244 who were SARS-CoV-2-negative (control group). Taste, smell, and appetite changes were assessed by self-reported visual analog scale. Preference for sweet, salty, umami, sour, bitter, and spicy were judged using the validated TASTE-26 questionnaire. RESULTS: Partial taste and smell losses were observed in both groups, while complete losses (ageusia and anosmia) were detected only in the case group. Moreover, only ageusia and anosmia were associated with SARS-CoV-2 positivity (P < 0.001, odds ratio of 14.5 and 27.5, respectively). Taste, smell, and appetite scores were more severely reduced in the case group (P < 0.0001). Multivariate analysis showed that anosmia and ageusia were the best predictors of SARS-CoV-2 positivity, followed by appetite loss and fever. Simultaneous losses of taste and smell but not taste preferences were associated with SARS-CoV-2 positivity (P < 0.01, odds ratio 2.28). CONCLUSIONS: Complete, but not partial, losses of taste and smell were the best predictors of SARS-CoV-2 infection. During the current COVID-19 pandemic, healthy persons with sudden simultaneous complete loss of taste and smell should be screened for COVID-19.

Neurological features and outcome in COVID-19: dementia can predict severe disease.

The COVID-19 pandemic has infected more than 22 million people worldwide. Although much has been learned about COVID-19, we do not know much about its neurological features and their outcome. This observational study was conducted on the patients of Imam Hossein Hospital, and 361 adult patients (214 males) with confirmed diagnosis of COVID-19 from March 5, 2020 to April 3, 2020, were enrolled. Data was gathered on age, sex, comorbidities, initial symptoms, symptoms during the disease course, neurological symptoms, and outcome. The mean age of the patients was 61.90 ± 16.76 years. The most common initial symptoms were cough, fever, and dyspnea. In 21 patients (5.8%), the initial symptom was neurological. History of dementia was associated with severe COVID-19 disease (odds ratio = 1.28). During the course of the disease, 186 patients (51.52%) had at least one neurological symptom, the most common being headache (109 [30.2%]), followed by anosmia/ageusia (69, [19.1%]), and dizziness (54, [15%]). Also, 31 patients had neurological complications (8.58%). Anosmia, ageusia, dizziness, and headache were associated with favorable outcome (P < 0.001), while altered mental status and hemiparesis were associated with poor outcome. The mortality rate of patients who had neurological complications was more than twice than that of patients without neurological complication (P = 0.008). Almost half of the patients experienced at least one neurological symptom, which may be the initial presentation of COVID-19. Dementia appears to be associated with severe COVID-19. Mortality was higher in patients with neurological complications, and these patients needed more intensive care.

Ageusia and anosmia, a common sign of COVID-19? A case series from four countries.

Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the tropism of the virus, have been recognized. That includes now the neurological manifestations and conditions, such as headache, encephalitis, as well as olfactory and taste disorders. We present a series of ten cases of RT-PCR-confirmed SARS-CoV-2-infected patients diagnosed with viral-associated olfactory and taste loss from four different countries.

Neurological complications in patients with SARS-CoV-2 infection: a systematic review.

BACKGROUND: As the COVID-19 pandemic unfolds worldwide, different forms of reports have described its neurologic manifestations. OBJECTIVE: To review the literature on neurological complications of SARS-CoV-2 infection. METHODS: Literature search performed following systematic reviews guidelines, using specific keywords based on the COVID-19 neurological complications described up to May 10th, 2020. RESULTS: A total of 43 articles were selected, including data ranging from common, non-specific symptoms, such as hyposmia and myalgia, to more complex and life-threatening conditions, such as cerebrovascular diseases, encephalopathies, and Guillain-Barré syndrome. CONCLUSION: Recognition of neurological manifestations of SARS-CoV-2 should be emphasized despite the obvious challenges faced by clinicians caring for critical patients who are often sedated and presenting other concurrent systemic complications.

Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying central nervous system involvement by SARS-CoV-2.