key: cord-0948142-gzgdm8qa
authors: Boscutti, A.; Delvecchio, G.; Pigoni, A.; Cereda, G.; Ciappolino, V.; Bellani, M.; Fusar-Poli, P.; Brambilla, P.
title: OLFACTORY AND GUSTATORY DYSFUNCTIONS IN SARS-CoV-2 INFECTION:
date: 2021-05-18
journal: Brain Behav Immun Health
DOI: 10.1016/j.bbih.2021.100268
sha: c2ae553d84e4a5a908362ccdd7b3a069ed76641a
doc_id: 948142
cord_uid: gzgdm8qa

BACKGROUND: Among Coronavirus Disease 2019 (COVID-19) manifestations, Olfactory (OD) and Gustatory (GD) Dysfunctions (OGD) have drawn considerable attention, becoming a sort of hallmark of the disease. Many have speculated on the pathogenesis and clinical characteristics of these disturbances; however, no definite answers have been produced on the topic. With this systematic review, we aimed to collect all the available evidence regarding the prevalence of OGD, the timing of their onset and their resolution, their rate of recovery and their role as diagnostic and prognostic tools for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: A systematic review comprising all the observational studies that reported the prevalence and/or the longitudinal trajectories of OGD in COVID-19 patients, as self-reported by patients or measured through objective psychophysical tests. RESULTS: After the selection process, 155 studies were included, with a total of 70920 patients and 105291 not-infected individuals. Prevalence reports were extremely variable across studies, with wide ranges for OD (0% - 98%) and GD (0-89%) prevalence. OGD occurred early during the disease course and only rarely preceded other symptoms; out of 30 studies with a follow-up time of at least 20 days, only in 5 studies OGD fully resolved in more than 90% of patients. OGD had low sensitivity and high specificity for SARS-CoV-2 infection; accuracy of OD and GD for infection identification was higher than 80% in 10 out of 33 studies and in 8 out of 22 studies considered, respectively. 28 out of 30 studies that studied the association between OGD and disease severity found how OGD were associated with lower rates of severe pneumonia, hospitalization and mortality. CONCLUSIONS: OGD seem to be highly prevalent in SARS-CoV-2 infection. They occur early, concomitantly with other symptoms and often persist after recovery, in some cases for months; whether a full recovery eventually occurs in all cases is not clear yet. OGD are good predictors of SARS-CoV-2 infection and are associated with a milder disease course.

Coronavirus disease 2019 (COVID- 19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); it has been declared a pandemic on 11 March 2020 by the World Health Organization 1 . As of April 2021, more than 150 million cases have been reported worldwide, causing over 3 milion deaths 2 and significant social and economic suffering.

While approximately half of those infected experience an asymptomatic disease course, the most common clinical manifestations are, in descending order of frequency, fever, cough, headache and sore throat 3 . Some patients, typically those of older age and/or suffering from other coexisting clinical conditions, may develop more severe forms of the disease, characterized by worsening of the respiratory dysfunction, acute respiratory distress syndrome, septic shock and, potentially, multi-organ failure 4 .

In addition to the clinical scenario described above, a variety of other "non-typical" manifestations have been described in patients with COVID-19, including neurological 5 , psychiatric and neuropsychiatric 6 , cardiovascular 7 , gastrointestinal 8 , dermatological 9 and pediatric 10 manifestations, which have been postulated to be the result of the trophism of human respiratory coronaviruses for multiple human tissues 11, 12 Among the extrapulmonary manifestations, the perceived high prevalence of olfactory and gustatory dysfunctions (OGD) had great resonance, even in the non-scientific community 13, 14 , eventually becoming a sort of "hallmark" of the disease. Consequently, the presence of OGD in COVID-19 patients has been consistently reported by authors from the early phases of the pandemic.

While a considerable amount of systematic reviews and meta-analyses have already been published on the topic (n=15) 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 , there are several reasons why we feel that our review can add valuable results for the readers.

First, the most updated database search was August 15 th 21 ; given the high rate of publication on COVID-19 30 , we expected that a high number of studies would have been published in the following months. Second, while all the meta-analyses cited above reported the prevalence of OGD, only few explored other aspects of these manifestations. In particular, only one meta-analysis collected data regarding the average duration of OGD 21 HISTOPATHOLOGICAL AND IMAGING FINDINGS" can be found after the "Conclusions"; it has to be intended as complementary section, separated from the main text.

We structured our systematic review on the basis of the Conducting Systematic Reviews and Meta-Analyses of Observational Studies of Etiology (COSMOS-E) guidelines 31 . The Preferred Reporting

Items for Systematic Reviews and Meta-Analyses (PRISMA) tool 32 was adopted for reporting.

The study design of each report was evaluated following the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines 33 . The following design were included: cohort (with or without a control group), case-control and cross-sectional studies. Case J o u r n a l P r e -p r o o f 5 series were excluded unless they provided follow-up data regarding OGD. Case reports or studies with sample < 10 were not considered for inclusion.

No restrictions were posed regarding the definition of the population of interest, except for the presence of any medical condition associated with OGD (e.g., Parkinson disease).

The only criterion for inclusion was SARS-CoV-2 positivity, defined as SARS-CoV-2 genome detection by real-time reverse transcription polymerase chain reaction (RT-PCR) or antigen detection on nasal, pharyngeal or respiratory sample. We also included studies that defined exposure as positivity to serological testing (irrespective of the assay employed) 34 .

Absence of exposure was defined as a negative result on the SARS-CoV-2 testing methods mentioned above. The presence of an unexposed control group was not necessary for a study to be included.

The outcome of interest was the occurrence of olfactory or gustatory disturbances. We did not pose limits regarding the way by which OGD were defined, and we included studies that assessed OGD through review of medical records, face to face or telephone clinical interviews, administration of web-or mobile application-based questionnaires. We also included studies that employed objective testing to assess OGD; no limitations were put regarding the type of psychophysical test adopted.

To identify potentially relevant records, PubMed, EMBASE and Web of Science databases were searched from December 1 st , 2019 to October 8 th , 2020. Only studies in English were considered.

The search was rerun weekly, and last updated on December 14 th .

The following string was used in PubMed and adapted for the other two databases: All the records were screened by title and abstract by two independent authors (AB and GD); on the second level of screening, full text of publications was evaluated by AB and VC; disagreements on study selection were resolved by consensus with the involvement of a third author (AP).

A preliminary data extraction form was designed by AB; it was then pilot tested on 15 randomly selected studies and fine-tuned accordingly. With the search being rerun on a weekly basis, data from newly included study were updated accordingly.

The following variables were extracted from each study included: 

After the selection process, a total of 155 records met the inclusion criteria. A total of 3394 papers were retrieved from databases; after duplication removal, 1667 records remained and were screened through title and abstract. 306 articles were considered for full text examination, and 152 were excluded ( Figure 1 ).

The studies characteristics and main findings are summarized below; a detailed report of all the records included is provided in a table format and can be found in the supplementary material section (Supplementary Material - Table 1 ).

When the study design was mislabeled by authors, the design reported was ignored and we labeled the study following the STROBE guidelines 33 . In this way, 91 (59%) studies were classified as cross-sectional, and 64 (41%) studies were labeled as cohort studies. Only one study had a casecontrol design 36 .

Since a meta-analysis outlined how OGD prevalence is significantly higher in Caucasians compared to Asian individuals 37 , we included the nationality of the population of the study among the variables collected. In our review, most studies (n=112) were performed in Europe or North America (n=41998 individuals), while only 13 records (n=6671) collected data on Asian populations.

A total of 58854 patients were included; 53196 were confirmed by RT-PCR (n=136 studies), while 5516 were defined by antibody detection (n=17 studies); in two records, both techniques were used 38, 39 . Given the heterogeneity in the way the studies reported disease severity, when possible, we tried to dichotomize disease severity as the need for hospitalization; otherwise, we labeled disease severity as reported by authors. Disease severity was characterized by 87 papers; 6036 J o u r n a l P r e -p r o o f individuals were managed as outpatients and/or were classified as having an asymptomatic or mild form of the disease (n=20 studies); 6207 were hospitalized and/or were classified as having a moderate to severe disease course (n=37 studies). Other studies (n=30, n=53196 individuals) considered a variably wide range of disease severity (from asymptomatic to severe, from outpatient course to ICU stay).

A total of 105291 healthy controls (defined either with RT-PCR or serology) were included (n = 57 studies).

A subjective report of OGD presence was collected by most studies (n=145 for OD, n=131 for GD);

in most cases, clinical information was gathered through retrospective review of medical records, face to face or telephone clinical interviews, administration of web-or mobile application-based questionnaires. However, in a minority of studies OGD presence was assessed through validated questionnaires (n=15). The Sino-Nasal Outcome Test (SNOT-22) 40 

Psychophysical validated evaluation of GD was performed in only 8 records 74, 65, 64, 63, 75, 76, 38, 59 . In 4 of them 74, 65, 64, 63, 75 , a four-item (sweet, salty, sour, bitter) test 77 was administrated, both in sample of hospitalized patients and a sample of outpatients (self-administered) 78 . "Taste strips", spoon-shaped filter paper strips impregnated with the four taste qualities 79 were used in 2 records 76,38 .

Aggregated prevalence (presence of either OD or GD) was given in 56 studies (36%), with a large inter-study variability (range: 1.5% 80 -91% 58 ).

Prevalence of OD was reported by 95 studies (62%), with extreme variability between studies (range: 0% 81 -98% 82 ).

Prevalence of GD was reported by 92 studies (59%); the large inter-study variability was confirmed also for this disturbance (range: 0% 81 -89% 83 ).

Considering only studies that performed psychophysical testing for OD (n=21), the lowest prevalence reported for OD was 19% 84 . In studies reporting both subjective and objective evaluations, those appeared to differ. In some cases, objective evaluation was more sensible to detect OD in those denying such disturbances 69 100 days after symptom onset) recovery rates were 54%, 89%, 88% and 84%, respectively.

In those who recovered, most studies reported that OGD resolved within 2 weeks after onset. In fact, mean or median duration of OGD was more than 14 days in only 3 studies 101,102,103 .

Of Sn, Sp, PLR and NLR were calculated for 51 studies; data are summarized as their range in Table 2, while the values for each study are reported in Supplementary Tables 3-5. In general, OGD had low sensitivity and high specificity for the diagnosis of SARS-CoV-2. Overall, accuracy of OGD (presence of OD or GD) for SARS-CoV-2 diagnosis was higher than 80% in 13 out of 22 studies, accuracy of OD was higher than 80% in 10 out of 33 studies; finally, accuracy of GD for diagnosis was higher than 80% in 8 out of 22 studies.

A total of 30 studies examined the relationship between OGD and severity of COVID-19; 12 did not find any significant association between the two variables 82, 75, 109, 54, 112, 84, 43, 88, 100, 90, 113, 114 .

In the others, the presence of OD was associated with a milder clinical course, and in particular with decreased risk of developing pneumonia 115 In two records, the presence of persistent OD was associated with increased need for hospitalization 64, 65 ; conversely, another study found that the frequency of smell function recovery was lower among non-hospitalized patients 85 .

Presence of GD was associated with decreased risk of developing pneumonia ( 87 ) and decrease need for hospitalization 83, 122, 86, 121 .

Finally, regarding aggregate OGD prevalence, in a study involving 12066 patients, ascendant hierarchical clustering was applied to generate four phenotypic clusters, one of which included OD and GD. This cluster was the one associated with the lowest rate of ICU admission and mortality 123 .

Similarly, in another record OGD was associated with lower rates of hospitalization and ICU admission 124 .

12 Overall, quality of evidence was low for most of the studies included. 11 studies were considered to have a very high risk of bias, 118 studies were classified as having a high risk of bias, while only 26 studies were labeled as low risk of bias.

The large number of studies included in this review reflects the magnitude of interest that the topic of chemosensory disturbances has attracted among the scientific community. In this review, we 

A key point that influences the results of prevalence studies is how outcomes are defined 125 . In the case of OGD, outcome could be defined as ascertained by subjective testing (clinical interviews, administration of questionnaires, retrospective medical chart screening) or objective testing, carried through psychophysical tests. Intuitively, it could be expected that psychophysical testing is more sensitive in detecting chemosensory dysfunction. However, from the reviewed studies it emerged that psychophysical testing was not always the most sensitive measure, since in some records 84, 76, 46 the prevalence of self-reported OGD was higher than the one derived from objective testing; in other cases, the opposite was true 69,61 , with psychophysical testing reporting higher prevalence.

Reports showed how absence of self-reported GD has high negative predictive value regarding the presence of GD as determined by objective testing 126 ; in this sense, since high negative predictive value is associated with high sensitivity, this finding suggests how based self-reported OGD could J o u r n a l P r e -p r o o f 13 be at least as reliable as objective methods. In fact, self-reported OD severity has been found to correlate fairly well with psychophysical testing OD scores 127 .

All the studies that employed objective testing used validated psychophysical tests, whose scores could be therefore expected to be highly reliable when compared with each other. However, Marino-Sanchez et al. 128 raised an important point regarding the replicability of tests across different countries. As an example, they refer to the study by Moein et al. 82 

Early anecdotal reports suggested how OGD could represent the first symptom of SARS-CoV-2 infection in the majority of cases 54 

In about one third of the included studies, a group of both SARS-CoV-2 negative (COVID-) and

SARS-CoV-2 positive (COVID-+) were included, thus allowing to test the efficacy of OGD as a diagnostic marker for the infection (Table 2, Table 3, and Table 4 ).

Overall, OGD were proven to have good accuracy in detecting the infection, even more so considering that these were symptoms often self-referred by patients; as a benchmark, clinical symptoms used to diagnose community acquired pneumonia all seem to perform worse than OGD 

Several studies showed how OGD were associated with SARS-CoV-2 infection independently from demographic, clinical or laboratory variables, ultimately supporting the notion by which OGD are specific symptoms of SARS-CoV-2 infection, and not the product of confounders. One of the most discussed candidates in the list of the potential confounders was the presence of nasal obstruction.

Regarding this last point, several of the studies included found nasal blockage to have a significant lower prevalence than OGD in SARS-CoV-2 patients. In particular, two papers from the GCCR 50,133 showed, through a principal component analysis, how OGD and nasal obstruction were mostly uncorrelated, and thus unlikely to demonstrate a causal relationship with each other.

Finally, various studies reported how OGD presence was associated with a generally milder disease characterized by a decreased need for hospitalization, lower rates of severe pneumonia or ARDS, decreased need for oxygen, intubation, and lower mortality rates. Among the hypotheses proposed, J o u r n a l P r e -p r o o f 15 the most common was the one suggesting that a strong immunological response in the lymphatic tissue of the nasal mucosa might be associated with higher rates of OGD, but also with a more effective immune response and thus with a lower incidence of complications 134 ; this hypothesis, however, has never been tested in pre-clinical or clinical settings to date and awaits confirmation.

Although the screening process was performed in a rigorous way, the rate of publications on the topic has been unprecedented; moreover, most authors performing clinical studies on SARS-CoV-2 have included, since the beginning of the pandemic, data about prevalence of OGD. Therefore, we could not exclude that some records could have been missed in the selection process.

Studies were highly heterogeneous in their design, with some being performed in hospital wards, others in emergencies department and others being cross-sectional studies on SARS-CoV-2 serology. However, we provided information regarding study design adopted, SARS-CoV-2 testing methodic employed, and the severity of patients studied. In several studies, assessment of OGD presence was carried out retrospectively through phone interviews or the administration of questionnaires weeks or month after the disease onset; in this case, the presence of recall bias could not be ruled out.

Finally, some of the reviewed studies investigated the rates of OGD resolution/recovery followingup the patients. However, while some of these studies clearly stated the attrition rate (number of lost at follow-up), others did not, ultimately limiting the reliability of OGD recovery rates reported.

From the reviewed studies it emerged how OGD are prevalent in patients with SARS-CoV-2 infection and how they can provide valuable information for early detection of the disease and for its prognostic stratification. Worrisome rates of OGD persistence are observed in the medium-term, and to date it is not clear whether these disturbances are fully reversible. Quality of the collected evidence was generally low, with most of the studies having a high risk of bias. Therefore, further studies are warranted on this topic, since OGD may represent one of the long-term complications of the disease. Of note, we did not find any original study regarding the etiopathogenesis of gustatory dysfunctions in SARS-CoV-2 infection; therefore, all the evidence presented below will focus on OD.

Many have suggested that the high rates of neurological complications seen in COVID-19 135 ,

including OGD, could be the consequence of SARS-CoV-2 neuroinvasive potential 136 .

All the preclinical studies conducted on murine models agree on the fact that the major target for SARS-CoV-2 infection is the olfactory non-neuronal epithelium, and specifically the sustentacular Specifically, the olfactory cleft anatomy was studied by 3 records, which reported thickening and obstruction of the olfactory cleft at the CT 153,154 , probably caused by mucosal edema as suggested by MRI T2 hyperintensity 154 ; this could be seen as a potential explanation of olfactory dysfunction in these patients, since the olfactory cleft represents the entry route of odorant molecules to the olfactory epithelium. Another study, however, reported no evidence of involvement of these olfactory areas 155 .

9 MRI studies reported relevant findings regarding olfactory bulb structure in anosmic COVID-19

patients.

Olfactory bulb dimensions were often found to be altered. A case report reported an enlargement along with an increase in T2 signal intensity, findings suggestive of edema 156 ; conversely, 5 studies reported a decrease in the size of the olfactory bulb 157, 158, 159, 160, 161 . Notably, out of these 5 studies, J o u r n a l P r e -p r o o f 18 three 157, 160, 161 were performed in patients with persistent (> 1 month in duration) anosmia. This finding seems to agree with the notion by which reduced dimension of the olfactory bulb in patients with post-infectious olfactory disorder is associated with longer duration of the chemosensory impairment 162, 155 .

Alterations in signal intensity within the olfactory bulb were also commonly reported, with diffuse hyperintense foci resembling microhemorrhages 157 , T2 FLAIR signal abnormalities 163, 164 and injury of the olfactory bulbs demonstrated by pre-contrast and post-contrast fat suppression T1W and STIR images 165 .

However, it must be outlined that olfactory bulbs hyperintensities in T2-FLAIR are a relative common finding in healthy subjects 166 ; for this reason, inclusion of a control group is warranted for a correct interpretation of these findings. In addition, given the small volumes of olfactory bulbs, high resolution sequences and objective intensity evaluations must be performed in order to avoid misinterpretation of paraphysiological findings. Still, the evidence seems to point out that the olfactory bodies might represent a key target of SARS-CoV-2 infection and a possible neuroimaging marker of olfactory dysfunctions in SARS-Cov-2 infection.

Involvement of the olfactory tracts was also reported, with evidence of bilateral T2 FLAIR and fat suppression hyperintensities and DWI abnormalities 159, 167 , suggestive of olfactory tract inflammatory neuropathy.

Finally, reports of alterations in cortical regions involved in processing of olfactory inputs were also found. Specifically, in two MRI studies on COVID-19 patients with anosmia, alterations of the right gyrus rectus were found in the form of FLAIR hyperintensity 168 and hemorrhage 169 . In addition, a study employing F-FDG brain PET imaging found rectal gyrus metabolism to be greatly reduced on Records screened n = 1667

Full-text articles assessed for eligibility n = 306

Full-text articles excluded, with reasons n = 152 No OGD outcome reported = 36 Editorial/comment/reply = 28 Wrong study design = 31 

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Severe Acute Respiratory Syndrome Coronavirus 2 Infects and Damages the Mature and Immature Olfactory Sensory Neurons of Hamsters

Innate immune signaling in the olfactory epithelium reduces odorant receptor levels: modeling transient smell loss in COVID-19 patients

COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice

A Mouse Model of SARS-CoV-2 Infection and Pathogenesis

Ionic conductances in sustentacular cells of the mouse olfactory epithelium

Elevated ACE-2 expression in the olfactory neuroepithelium: Implications for anosmia and upper respiratory SARS-CoV-2 entry and replication

Expression of the SARS-CoV-2

Cells of the Olfactory Epithelium: Identification of Cell Types and Trends with Age

Proinflammatory Cytokines in the Olfactory Mucosa Result in COVID-19 Induced Anosmia

Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia

Olfactory transmucosal SARS-CoV-2 invasion as port of Central Nervous System entry in COVID-19 patients

First ultrastructural autoptic findings of sars-cov-2 in olfactory pathways and brainstem

Inflammatory olfactory neuropathy in two patients with COVID-19

Ultrastructural evidence of direct viral damage to the olfactory complex in patients testing positive for SARS-COV-2

Neuropathology of patients with COVID-19 in Germany: a post-mortem case series

Isolated olfactory cleft involvement in SARS-CoV-2 infection: prevalence and clinical correlates

Olfactory Cleft Measurements and COVID-19-Related Anosmia. Otolaryngol -Head Neck Surg (United States)

Paranasal sinuses computed tomography findings in anosmia of COVID-19

Bilateral transient olfactory bulb edema during COVID-19-related anosmia

Olfactory Bulb MRI and Paranasal Sinus CT Findings in Persistent COVID-19 Anosmia

COVID-19-induced anosmia associated with olfactory bulb atrophy

Anosmia and olfactory tract neuropathy in a case of COVID-19

Olfactory bulb and mucosa abnormalities in persistent COVID-19-induced anosmia: a magnetic resonance imaging study

Olfactory Bulb Atrophy in a Case of COVID-19 with Hyposmia

Loss of smell in COVID-19 patients: MRI data reveals a transient edema of the olfactory clefts

Olfactory bulb signal abnormality in patients with COVID-19 who present with neurologic symptoms

Magnetic resonance imaging of COVID-19 anosmic patients reveals abnormalities of the olfactory bulb: Preliminary prospective study

Anosmia in COVID-19 associated with injury to the olfactory bulbs evident on MRI

MR Imaging of the Olfactory Bulbs in Patients with COVID-19 and Anosmia: How to Avoid Misinterpretation

SARS-CoV-2 Related Encephalitis: MRI Pattern of the Olfactory Tract Involvement

Magnetic resonance imaging alteration of the brain in a patient with coronavirus disease 2019 (COVID-19) and anosmia

Olfactory gyrus intracerebral hemorrhage in a patient with COVID-19 infection

Olfactory and gustative disorders for the diagnosis of COVID-19

Symptom Criteria for COVID-19 Testing of Heath Care Workers

Loss of Taste and Smell as Distinguishing Symptoms of COVID-19

Risk of COVID-19 in health-care workers in Denmark: an observational cohort study

Loss of Smell and Taste Among Healthcare Personnel Screened for Coronavirus

Symptoms associated with a positive result for a swab for SARS-CoV-2 infection among children in Alberta

Seroprevalence of Antibodies Against SARS-CoV-2 Among Health Care Workers in Mumbai, India

Symptoms and Transmission of SARS-CoV-2 among Children-Utah and Wisconsin

Real-time tracking of self-reported symptoms to predict potential COVID-19

Longitudinal symptom dynamics of COVID-19 infection

Smell and taste symptom-based predictive model for COVID-19 diagnosis

Seroprevalence of SARS-CoV-2-Specific Antibodies among Adults

Prevalence of SARS-CoV-2 IgG antibodies in an area of North-eastern Italy with a high incidence of COVID-19 cases: a population-based study

Headache characteristics in COVID-19 pandemic-a survey study

Prevalence of Antibodies to SARS-CoV-2 in Italian Adults and Associated Risk Factors

Nationwide seroprevalence of SARS-CoV-2 and identification of risk factors in the general population of the Netherlands during the first epidemic wave

The role of self-reported olfactory and gustatory dysfunction as a screening criterion for suspected COVID-19

Contribution of anosmia and dysgeusia for diagnostic of COVID-19 in outpatients

Symptoms and symptom clusters associated with SARS-CoV-2 infection in community-based populations: Results from a statewide epidemiological study. medRxiv Prepr Serv Heal Sci

Self-reported symptoms from exposure to Covid-19 provide support to clinical diagnosis, triage and prognosis: An exploratory analysis

Symptoms in health care workers during the covid-19 epidemic. A cross-sectional survey

Prospective Study in 355 Patients With Suspected COVID-19 Infection: Value of Cough, Subjective Hyposmia, and Hypogeusia

Post lockdown COVID-19 seroprevalence and circulation at the time of delivery

SARS-CoV-2 exposure, symptoms and seroprevalence in healthcare workers in Sweden

Ocular involvement in coronavirus disease 2019 (COVID-19): a clinical and molecular analysis

Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response

Self-Collected versus Healthcare Worker-Collected Swabs in the Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2

Strong associations and moderate predictive value of early symptoms for SARS-CoV-2

Main symptoms in patients presenting in the COVID-19 period