Headache, Loss of Smell, and Visual Disturbances: Symptoms of SARS-CoV-2 Infection? A Case Report.

OBJECTIVE: The purpose of this case report is to describe the main components of the history and physical examination that led to idiopathic intracranial hypertension differential diagnosis, which initially was investigated as COVID-19. METHODS (CASE DESCRIPTION): A 28-year-old woman complaining of constant headache and loss of smell and taste was suspected as SARS-CoV-2 infection by her general practitioner. She underwent 3 molecular swab tests, all negative, then decided to seek her physical therapist for relieving headache. RESULTS: The full cranial nerve examination revealed impaired olfactory (CNI), abducens (CN VI), and facial (CN VII) nerves, leading the physical therapist to refer the patient to a neurosurgeon for a suspected central nervous system involvement. The neurosurgeon prescribed a detailed MRI and an ophthalmologic examination, which allowed for the final diagnosis of idiopathic intracranial hypertension. CONCLUSION: An urgent lumbo-peritoneal shunting surgery resolved the patient's symptoms and saved her sight. Despite the ongoing COVID-19 pandemic, health care professionals must pay attention to properly investigating patients' signs and symptoms using comprehensive clinical reasoning, considering the screening for referral to specialist medical attention. IMPACT: A thorough physical examination is required for every patient even if patients' signs and symptoms are in line with apparent common and widespread pathologies. Cranial nerve evaluation is an essential component of the physical therapist assessment and decision-making process. The ongoing pandemic highlighted the fundamental assistance of physical therapists toward physicians in the screening and management of musculoskeletal diseases.

Long COVID and especially headache syndromes.

PURPOSE OF REVIEW: This is an expert overview on recent literature about the complex relationship between coronavirus disease 2019 (COVID-19) and headache. RECENT FINDINGS: Long COVID is a clinical syndrome characterized by the presence of persistent symptoms following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Headache is one of the most common symptoms and is described most often as throbbing pain, associated with photo and phonofobia and worsening with physical exercise. In acute COVID-19, headache is usually described as moderate or severe, diffuse and oppressive although sometimes it has been described with a migraine-like phenotype, especially in patients with a previous history of migraine. Headache intensity during acute phase seems to be the most important predictor of duration of headache over time. Some COVID-19 cases can be associated with cerebrovascular complications, and red flags of secondary headaches (e.g. new worsening or unresponsive headache, or new onset of neurological focal signs) should be urgently investigated with imaging. Treatment goals are the reduction of number and intensity of headache crises, and the prevention of chronic forms. SUMMARY: This review can help clinicians to approach patients with headache and infection from SARS-CoV-2, with particular attention to persistent headache in long COVID.

Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

Cross-sectional, hospital-based analysis of headache types using ICHD-3 criteria in the Middle East, Asia, and Africa: the Head-MENAA study.

BACKGROUND: Headaches are frequent neurological disorders that are yet to be unveiled and treated comprehensively worldwide. Bearing in mind that the distribution of headache subtypes in neurology clinics (NC) is essential for planning appropriate diagnostic and therapeutic approaches, the primary goals of this multi-centric study are to carry out inter-regional comparisons by using current diagnostic criteria with evaluations of neurologists to delineate headache burden. METHODS: A cross-sectional study between April 1 and May 16, 2022 was conducted with the participation of 13 countries from the Middle East, Asia, and Africa. Patients were included in the study on a specific day each week during five consecutive weeks. All volunteers over the age of 18 and whose primary cause for admission was headache were examined. The patients admitted to NC or referred from emergency services/other services were evaluated by neurologists by means of the International Classification of Headache Disorders (ICHD-3) criteria. RESULTS: Among the 13,794 patients encountered in NC, headache was the primary complaint in 30.04%. The headache patients' mean age was 42.85 ± 14.89 (18-95 years), and 74.3% were female. According to the ICHD-3 criteria, 86.7% of the main group had primary headache disorders, 33.5% had secondary headaches, 4% had painful cranial neuropathies along with other facial and headaches, and 5.2% had headaches included in the appendix part showing some overlapping conditions. While the most common primary headache was migraine without aura (36.8%), the most common secondary headache was medication-overuse headache (MOH) (9.8%). Headaches attributed to COVID-19, its secondary complications, or vaccines continue to occur at rates of 1.2%-3.5% in current neurology practice. Pain severity was significantly lower in Ivory Coast and Sudan than in Türkiye, Turkish Republic of Northern Cyprus, Iran, Egypt, Senegal, Tatarstan, and Azerbaijan (p < 0.001). CONCLUSIONS: The study showed that migraine is still the most common motive for admissions to NC in different regions. Furthermore, MOH, an avoidable disorder, is the most common secondary headache type and appears to be a significant problem in all regions. Remarkably, pain perception differs between regions, and pain intensity is lower in Africa than in other regions.

Racial/Ethnic Disparities in Post-acute Sequelae of SARS-CoV-2 Infection in New York: an EHR-Based Cohort Study from the RECOVER Program.

BACKGROUND: Compared to white individuals, Black and Hispanic individuals have higher rates of COVID-19 hospitalization and death. Less is known about racial/ethnic differences in post-acute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: Examine racial/ethnic differences in potential PASC symptoms and conditions among hospitalized and non-hospitalized COVID-19 patients. DESIGN: Retrospective cohort study using data from electronic health records. PARTICIPANTS: 62,339 patients with COVID-19 and 247,881 patients without COVID-19 in New York City between March 2020 and October 2021. MAIN MEASURES: New symptoms and conditions 31-180 days after COVID-19 diagnosis. KEY RESULTS: The final study population included 29,331 white patients (47.1%), 12,638 Black patients (20.3%), and 20,370 Hispanic patients (32.7%) diagnosed with COVID-19. After adjusting for confounders, significant racial/ethnic differences in incident symptoms and conditions existed among both hospitalized and non-hospitalized patients. For example, 31-180 days after a positive SARS-CoV-2 test, hospitalized Black patients had higher odds of being diagnosed with diabetes (adjusted odds ratio [OR]: 1.96, 95% confidence interval [CI]: 1.50-2.56, q<0.001) and headaches (OR: 1.52, 95% CI: 1.11-2.08, q=0.02), compared to hospitalized white patients. Hospitalized Hispanic patients had higher odds of headaches (OR: 1.62, 95% CI: 1.21-2.17, q=0.003) and dyspnea (OR: 1.22, 95% CI: 1.05-1.42, q=0.02), compared to hospitalized white patients. Among non-hospitalized patients, Black patients had higher odds of being diagnosed with pulmonary embolism (OR: 1.68, 95% CI: 1.20-2.36, q=0.009) and diabetes (OR: 2.13, 95% CI: 1.75-2.58, q<0.001), but lower odds of encephalopathy (OR: 0.58, 95% CI: 0.45-0.75, q<0.001), compared to white patients. Hispanic patients had higher odds of being diagnosed with headaches (OR: 1.41, 95% CI: 1.24-1.60, q<0.001) and chest pain (OR: 1.50, 95% CI: 1.35-1.67, q < 0.001), but lower odds of encephalopathy (OR: 0.64, 95% CI: 0.51-0.80, q<0.001). CONCLUSIONS: Compared to white patients, patients from racial/ethnic minority groups had significantly different odds of developing potential PASC symptoms and conditions. Future research should examine the reasons for these differences.

[The Importance of Differential Diagnosis During Pandemic: A Case Report with Coexistence of COVID-19, Brucellosis and Crimean-Congo Hemorrhagic Fever]. / Pandemi Döneminde Ayirici Taninin Önemi: COVID-19, Bruselloz ve Kirim-Kongo Kanamali Atesi Birlikteligi Olan Bir Olgu Sunumu.

The coronavirus disease-2019 (COVID-19) pandemic, which affects millions of people around the world, has been affecting our country since March 2020. The fact that the symptoms such as fever, myalgia, headache, joint pain which are common in COVID-19 patients are quite similar to the symptoms of diseases such as Crimean-Congo hemorrhagic fever (CCHF) and Brucellosis. This may cause a diagnostic confusion in regions where these diseases are seen as endemic. In this report, a patient hospitalized with a pre-diagnosis of COVID-19 and diagnosed with acute Brucellosis, CCHF and COVID-19 during followup was presented. A 31-year-old female patient living in a rural area admitted to the emergency service with complaints of fever, weakness, headache, and body/joint pain. Physical examination revealed a temperature of 38.3°C, a pulse rate of 102/minute, and a peripheral capillary oxygen saturation of 97% in room air. The system examination was normal. In the laboratory findings, an increase in liver enzymes and acute phase reactants was observed and the platelet count was at the lower limit of the normal range. In terms of COVID-19, no involvement compatible with COVID-19 was detected in the thorax computed tomography (CT) of the patient whose nasopharyngeal and oropharyngeal mixed swab samples were taken.The patient was transferred to our infectious diseases service with a pre-diagnosis of COVID-19 and CCHF. Serum samples were sent to the Public Health Agency Microbiology Reference Laboratory Department (PHA-MRLD) for CCHF diagnostic tests and supportive treatment was started. Brucella Rose Bengal and Coombs' immuncapture (1/1280 titer) tests were found as positive in the patient, who was examined for brucellosis because of living in a rural area and having a history of consuming fresh dairy products. In the tests performed at PHA-MRLD, CCHF-specific IgM positivity and the presence of viral RNA were detected. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reverse-transcriptase polymerase chain reaction (RT-PCR) test was negative. For Brucellosis, doxycycline and rifampicin were added to the treatment of the patient whom was given supportive therapy for CCHF. In the followup, the patient's fever was persisting and loss of taste and smell complaint developed. In this context, COVID-19 test was repeated and resulted as positive. Upon this, hydroxychloroquine sulfate treatment was started due to the recommendation of the current Ministry of Health Scientific Committee Guide. No new infiltration was detected in the chest radiography of the patient. The patient's fever subsided during follow-up and laboratory findings improved. The treatment of brucellosis was completed to eight weeks at the outpatient clinic. No problems were detected in the follow-up. This report was prepared because of a case with simultaneous brucellosis, CCHF and COVID-19 infections which could not be encountered in the literature review. As a result; in regions such as our country where both brucellosis and CCHF are seen as endemic, it is very important to keep these diseases in mind in the differential diagnosis of COVID-19 infection.

Long COVID active case detection initiative among COVID-19 patients in Port Dickson, Malaysia: a retrospective study on the positive outcomes, the proportion of patients with long COVID and its associated factors.

Background: Long COVID is new or ongoing symptoms at four weeks or more after the start of acute COVID-19. However, the prevalence and factors associated with long COVID are largely unknown in Malaysia. We aim to determine the proportion and factors associated with long COVID among COVID-19 patients in Port Dickson, Malaysia. The positive outcomes of our long COVID active detection initiative were also described. Methods: This was a retrospective analysis of long COVID data collected by the Port Dickson District Health Office between 1 September 2021 to 31 October 2021. Monitoring long COVID symptoms was our quality improvement initiative to safeguard residents' health in the district. The study population was patients previously diagnosed with COVID-19 who resided in Port Dickson. The inclusion criteria were adults aged 18 years and above and were in the fifth week (day 29 to 35) post-COVID-19 diagnosis during the data collection period. We called all consecutive eligible patients to inquire regarding long COVID symptoms. Long COVID was defined as new or ongoing symptoms lasting more than 28 days from the date of positive SARS-CoV-2 by polymerase chain reaction test. Binary multivariate logistic regression was conducted to determine factors associated with long COVID. Results: Among 452 patients, they were predominantly male (54.2%), Malays (68.8%) and aged 18-29 years (58.6%). A total of 27.4% (95% CI [23.4-31.8]) of patients experienced long COVID symptoms and were referred to government clinics. The most frequent long COVID symptoms experienced were fatigue (54.0%), cough (20.2%), muscle pain (18.5%), headache (17.7%) and sleep disturbance (16.1%). Females, patients with underlying cardiovascular disease, asthma and chronic obstructive airway disease, those who received symptomatic care, and patients with myalgia and headaches at COVID-19 diagnosis were more likely to have long COVID. Three patients with suspected severe mental health problems were referred to the district psychologist, and ten patients with no/incomplete vaccination were referred for vaccination. Conclusion: Long COVID is highly prevalent among COVID-19 patients in Port Dickson, Malaysia. Long-term surveillance and management of long COVID, especially among the high-risk groups, are needed as we transition to living with COVID-19.

Headache attributed to SARS-CoV-2 infection, vaccination and the impact on primary headache disorders of the COVID-19 pandemic: A comprehensive review.

OBJECTIVE: The objective is to summarize the knowledge on the epidemiology, pathophysiology and management of secondary headache attributed to SARS-CoV-2 infection and vaccination; as well as to delineate their impact on primary headache disorders. METHODS: This is a narrative review of the literature regarding primary and secondary headache disorders in the setting of COVID-19 pandemic. We conducted a literature search in 2022 on PubMed, with the keywords "COVID 19" or "vaccine" and "headache" to assess the appropriateness of all published articles for their inclusion in the review. RESULTS: Headache is a common and sometimes difficult-to-treat symptom of both the acute and post-acute phase of SARS-CoV-2 infection. Different pathophysiological mechanisms may be involved, with the trigeminovascular system as a plausible target. Specific evidence-based effective therapeutic options are lacking at present. Headache attributed to SARS-CoV-2 vaccinations is also common, its pathophysiology being unclear. People with primary headache disorders experience headache in the acute phase of COVID-19 and after vaccination more commonly than the general population. Pandemic measures, forcing lifestyle changes, seemed to have had a positive impact on migraine, and changes in headache care (telemedicine) have been effectively introduced. CONCLUSIONS: The ongoing COVID-19 pandemic is a global challenge, having an impact on the development of secondary headaches, both in people with or without primary headaches. This has created opportunities to better understand and treat headache and to potentiate strategies to manage patients and ensure care.

Refractory Headaches.

Medication overuse headache (MOH), new daily persistent headache (NDPH), and persistent refractory headache attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection represent a significant burden in terms of disability and quality of life, and a challenge in terms of definition, pathophysiology, and treatment. Regarding MOH, prevention without withdrawal is not inferior to prevention with withdrawal. Preventive medications like topiramate, onabotulinumtoxinA, and calcitonin gene-related peptide (CGRP) monoclonal antibodies improve chronic migraine with MOH regardless of withdrawal. The differential diagnosis of NDPH is broad and should be carefully examined. There are no guidelines for the treatment of NDPH, but options include a short course of steroids, nerve blocks, topiramate, nortriptyline, gabapentin, CGRP monoclonal antibodies, and onabotulinumtoxinA. The persistence of headache 3 months after SARS-CoV2 infection is a predictor of poor prognosis.

Secondary Headache Disorders: Approach, Workup, and Special Considerations for Select Populations.

Headache is one of the most common diagnoses in neurology. A thorough understanding of the clinical presentation of secondary headache, which can be life-threatening, is critical. This review provides an overview of the diagnostic approach to a patient with headache, including discussion of "red," "orange," and "green" flags. We emphasize particular scenarios to help tailor the clinical workup to individual circumstances such as in pregnant women, when particular attention must be paid to the effects of blood pressure and hypercoagulability, as well as in older adults, where there is a need for higher suspicion for an intracranial mass lesion or giant cell arteritis. Patients with risk factors for headache secondary to alterations in intracranial pressure, whether elevated (e.g., idiopathic intracranial hypertension) or decreased (e.g., cerebrospinal fluid leak), may require more specific diagnostic testing and treatment. Finally, headache in patients with COVID-19 or long COVID-19 is increasingly recognized and may have multiple etiologies.

Long COVID headache.

Headache is among the most frequent symptoms persisting or newly developing after coronavirus disease 2019 (COVID-19) as part of the so-called long COVID syndrome. The knowledge on long COVID headache is still limited, however growing evidence is defining the features of this novel condition, in particular regarding clinical characteristics, some pathophysiological mechanisms and first treatment recommendations. Long COVID headache can present in the form of worsening of a preexisting primary headache, or, more specifically, in the form of a new (intermittent or daily) headache starting during the acute infection or after a delay. It often presents together with other long COVID symptoms, most frequently with hyposmia. It can manifest with a migrainous or, more frequently, with a tension-type-like phenotype. Persistent activation of the immune system and trigeminovascular activation are thought to play a role. As there are virtually no treatment studies, treatment currently is largely guided by the existing guidelines for primary headaches with the corresponding phenotype. The present report, a collaborative work of the international group of the Junior Editorial Board of The Journal of Headache and Pain aims to summarize the most recent evidence about long COVID headache and suggests approaches to the diagnosis and treatment of this disorder.

Rotavirus meningitis in an adult with transient aphasia.

We identified an additional case of documented Rotavirus meningitis in an adult with full medical history. A previously healthy 37-year-old patient presented herself for transient aphasia associated with fever and headaches at the end of a one-week history of gastroenteritis. Cerebrospinal fluid (CSF) analysis revealed lymphocytic meningitis, and treatment with aciclovir was initiated. Rotavirus A reverse transcription-polymerase chain reaction (RT-PCR) was positive in CSF and the patient's stools in favor of Rotavirus meningitis. Testing for other viruses was negative. Magnetic resonance imaging (MRI) showed no signs of encephalitis. Aphasia was resolutive in less than 12 hours, and no neurological symptoms relapsed. All symptoms evolved favorably despite aciclovir discontinuation. Viral sequencing methods have recently identified unexpected viruses as potential causative agents in meningitis, including Rotavirus. We confirm the detectability of Rotavirus in the analysis of CSF in the context of Rotavirus gastroenteritis in an adult. This case suggests postviral headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome may be linked to previously undetected direct viral infection of the central nervous system. Therefore, clinicians should consider Rotavirus meningitis in diagnosing meningitis associated with gastroenteritis in adults.

The impact of headache symptoms in a population of Italian university students during the COVID period: an observational study based on 4926 cases.

We conducted an observational study of 4926 university students from all over Italy and different university courses, including health areas. Students were contacted through the most popular social networks and some student's course representatives also acted as intermediaries, from June 1 to August 31, 2021. A questionnaire has been carried out using "Google Forms" and MIDAS. The study confirmed how the headache was widespreaded among the student population and how much it was underestimated (only one-fifth of the interviewees had been to a specialist/headache center). The negative impact of habitual headache on school performance was confirmed by the attendance on courses and the overall study performance. The clinical phenomenon might have been impacted by the pandemic period and its changes in lifestyle, in the study methodology, and due to the stress increase. Finally, the means used in the study were very satisfactory: the use of peers of the interviewees and the social networks, obtaining a broad acceptance of the study and possibly offering a method which is likely to be used in the future. Students presenting habitual headaches must be aware of their condition and the need to search for an appropriate diagnosis and treatment.

Prevalence of migraine headaches and their impact on the academic performance of Sudanese medical students using ID-Migraine test as a screening tool: A cross-sectional study.

BACKGROUND: Migraine-and episodic headache-is one of the most common types of primary headache. Migraine is considered a serious health problem that affects the quality of life. During university life, students often report increased levels of stress, depression, anxiety, and irregular sleep, all of which are associated with migraines. Our aim was to determine the prevalence of migraine headaches among medical campus students at the University of Khartoum, Sudan. Based on available data, migraine is on the rise in both general populations as well as in university students. METHODS: This is a cross-sectional study. The study population was composed of students registered to the Faculty of Medicine, Dentistry, and Pharmacy at Khartoum University in the academic years of 2020-2021. Out of these, 318 of them accepted to participate. Participants who had two or more headaches in the last 3 months formed the headache group. Afterwards, two preliminary questions were applied to the headache group and participants with at least one affirmative response were asked to perform the validated ID-Migraine™ test. RESULTS: The mean age of 318 students participating in the study was 19.23 ± 1.84 (17-39 years), with adolescents:adult ratio being 2.5:1. A total of 1613 students (43.7%) had at least two headaches in the last 3 months. Migraine-type headache was detected in 266 subjects (7.2%) based on the ID-Migraine™ test. Of the migraine group, 72 were male (27.1%) and 194 were female (72.9%). There was no significant difference in migraine prevalence between adolescent and adult age groups. CONCLUSIONS: With prevalence similar to adults, primary care physicians should be aware of the probability of migraine headaches in university students in order to maintain a successful school performance.

SARS-CoV-2 infection in children and adolescents: a Brazilian experience.

OBJECTIVE: To describe clinical and epidemiological aspects of children and adolescents infected with the SARS-CoV-2 in the Municipality of Taubaté, SP, from March to November 2020. METHODS: Cross-sectional study with secondary data obtained from the Epidemiological Surveillance System about confirmed cases in city residents and from medical records of patients who were treated in hospitals in Taubaté, aged between 0 and 19 years. Chi-square and Student's t tests were used for comparisons. RESULTS: 677 cases in the studied age range were reported during the study period, corresponding to 10.1% of cases reported in the municipality. The rapid antibody test was the most used to confirm infection, followed by RT-PCR and serology. Symptoms were described in 57.7% of the cases, mainly fever and cough. Diarrhea was associated with age below 4 years, while fever, cough, headache, odynophagia, ageusia, anosmia, myalgia, and dyspnea were associated with an age ranging from 10 to 19 years. In the study period, there were no deaths from COVID-19 of residents of the municipality in the age group from 0 to 19 years. CONCLUSIONS: The study was able to identify the proportion of involvement of COVID-19 in children and adolescents in the city, and the disease had a mild evolution. The main symptoms were fever and cough, but mainly diarrhea in younger children, and headache, odynophagia, anosmia, ageusia, and myalgia in adolescents.

Clinical manifestations, treatment options, and comorbidities in COVID-19 relapse patients: A systematic review.

INTRODUCTION: Interest revolving around coronavirus disease 2019 (COVID-19) reinfection is escalating rapidly. By definition, reinfection denotes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), PCR redetection, and COVID-19 recurrence within three months of the initial symptoms. The main aim of the current systematic review was to evaluate the features of COVID-19 relapse patients. MATERIALS AND METHODS: For this study, we used a string of terms developed by a skilled librarian and through a systematical search in PubMed, Web of Science, and Embase for eligible studies. Clinical surveys of any type were included from January 2019 to March 2021. Eligible studies consisted of two positive assessments separated by a negative result via RT-PCR. RESULTS: Fifty-four studies included 207 cases of COVID-19 reinfection. Children were less likely to have COVID-19 relapse. However, the most patients were in the age group of 20-40 years. Asthenia (66.6%), headache (66.6%), and cough (54.7%) were prevalent symptoms in the first SARS-CoV-2 infection. Asthenia (62.9%), myalgia (62.9%), and headache (61.1%) were most frequent in the second one. The most common treatment options used in first COVID-19 infection were lopinavir/ritonavir (80%), oxygen support (69.2%), and oseltamivir (66.6). However, for the treatment of second infection, mostly antibiotics (100%), dexamethasone (100%), and remdesivir (80%) were used. In addition, obesity (32.5%), kidney failure (30.7%), and hypertension (30.1%) were the most common comorbidities. Unfortunately, approximately 4.5% of patients died. CONCLUSION: We found the potency of COVID-19 recurrence as an outstanding issue. This feature should be regarded in the COVID-19 management. Furthermore, the first and second COVID-19 are similar in clinical features. For clinically practical comparison of the symptoms severity between two epochs of infection, uniform data of both are required. We suggest that future studies undertake a homogenous approach to establish the clinical patterns of the reinfection phenomena.

Coronavirus Disease 2019, Eye Pain, Headache, and Beyond.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19), emerged in December 2019 and became a devastating pandemic. Although its respiratory effects can be deadly and debilitating, it can lead to other systemic disorders, such as those causing eye pain and headache. This literature review aims to describe presentations of eye pain and headache in relation to COVID-19, with an emphasis on how these disorders help us to understand the pathophysiology of COVID-19. EVIDENCE ACQUISITION: Literature was mined from the PubMed database using the key terms: "eye pain," "conjunctivitis," "episcleritis," "optic neuritis," "migraine," and "headache" in conjunction with "COVID-19" and "SARS-CoV-2." With the exception of general background pathology, articles that predated 2006 were excluded. Case reports, literature reviews, and meta-analyses were all included. Where SARS-CoV-2 research was deficient, pathology of other known viruses was considered. Reports of ocular manifestations of vision loss in the absence of eye pain were excluded. The primary search was conducted in June 2021. RESULTS: The literature search led to a focused review of COVID-19 associated with conjunctivitis, episcleritis, scleritis, optic neuritis, and myelin oligodendrocyte glycoprotein-associated optic neuritis. Four distinct COVID-19-related headache phenotypes were identified and discussed. CONCLUSIONS: Eye pain in the setting of COVID-19 presents as conjunctivitis, episcleritis, scleritis, or optic neuritis. These presentations add to a more complete picture of SARS-CoV-2 viral transmission and mechanism of host infection. Furthermore, eye pain during COVID-19 may provide evidence of hypersensitivity-type reactions, neurovirulence, and incitement of either novel or subclinical autoimmune processes. In addition, investigation of headaches associated with COVID-19 demonstrated 4 distinct phenotypes that follow third edition of the International Classification of Headache Disorders categories: headaches associated with personal protective equipment, migraine, tension-type headaches, and COVID-19-specific headache. Early identification of headache class could assist in predicting the clinical course of disease. Finally, investigation into the COVID-19-associated headache phenotype of those with a history of migraine may have broader implications, adding to a more general understanding of migraine pathology.