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Ophthalmic manifestations in the COVID-19 clinical spectrum

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Purpose: The aim of this study was to determine the frequency and various types of ophthalmic manifestation of patients with COVID-19. Methods: This is a prospective observational study conducted on patients with SARS-Co-V-2 infection, at a dedicated tertiary COVID-19 hospital in South India from April 1 to July 31, 2020. At the time of their admission to the COVID hospital, demographic data such as name, age, sex was recorded. A thorough history regarding the onset, duration, progression, nature of symptoms and its associated factors, medication history, treatment history were elicited and documented. Ocular examination was performed under torchlight by an ophthalmologist posted for COVID duty. Further investigations including imaging were sought for, depending on clinical indications. Serial follow-up examinations of all patients were carried out every 72 hours or when patients complained of any ocular symptoms whichever earlier, until discharge. All relevant data were compiled and statistically analyzed. Results: A total of 2742 patients were examined. Of them, 1461 (53.28%) were males and 1281 (46.72%) were females. The mean age (±SD) was 39.46 ± 17.63 years. None of the patients in our study had any ocular symptoms or signs as the presenting complaint at the time of their admission. On subsequent follow-up, only 20 (0.72%) developed ocular manifestations, of which 19 (95%) had features suggestive of Bilateral viral conjunctivitis. However, 1 (5%) patient had orbital cellulitis secondary to pansinusitis. Conclusion: Ophthalmic manifestations in the clinical spectrum of COVID-19 infection are uncommon and unlikely to be the presenting clinical impression. However, it has broadened our view to a wider spectrum of COVID-19 presentations enhancing our clinical acumen for staunch detection of COVID-19 suspects in our daily practice, augmenting early diagnosis and management and also break the chain of transmission for the greater good of humanity.
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© 2021 Indian Journal of Ophthalmology | Published by Wolters Kluwer - Medknow
Expedited Publication, Original Article
Ophthalmic manifestations in the COVID-19 clinical spectrum
Kiran Kumar K, Sampritha UC, Akshata A Prakash, Karishma Adappa, Chandraprabha S, Neeraja TG,
Guru Prasad N S, Jessica Basumatary, Suresh Babu Gangasagara, Sujatha Rathod B L,
Chakravarthy Raghunathan Jayanthi1
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www.ijo.in
DOI:
10.4103/ijo.IJO_3037_20
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Purpose:               
 Methods:   
          
   
              


           
     
   
Results:        
                
               
             
         
Conclusion:




Key words:
Department of Ophthalmology, Regional Institute of Ophthalmology,
1


 


22‑Sep‑2020 Revision:
 21‑Jan‑2021 

      
 

   
 
[1] It has human‑to
human transmission via various routes namely aerosol,
[2]
has varied symptomatology and presentations, with majority

    
[3] Fatal



[1,4]   
 This
    
   
  [6]    
    [7,8]


   


    
    


Methods

    

Cite this article as: Kumar KK, Sampritha UC, Prakash AA, Adappa K,
Chandraprabha S, Neeraja TG, et al. Ophthalmic manifestations in the
COVID-19 clinical spectrum. Indian J Ophthalmol 2021;69:691-4.
This is an open access journal, and articles are distributed under the terms of
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which allows others to remix, tweak, and build upon the work non‑commercially,
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the identical terms.
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Figure 2: Case of orbital cellulitis showing lid edema, chemosis
692  Volume 69 Issue 3
 

 



[9]

 

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guidelines of the Ministry of Health and Family Welfare of

[10]
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Results

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    
  
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    
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      
    









Discussion



[11,12] Uniformly, none of the patients in


features developed it later during their stay at the hospital as

In a 2003 Singaporean study, Loon et al. sampled tears from


      
[13] In a


[14]



 
    
     
Figure 1: (a) Follicular conjunctivitis. (b) Follicular conjuctivitis
b
a
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 et al 693
[7]
  
et al[12]
et al.

[8]


    



  


      
    
[16]
    
       [17]
   

    

   




   




 
     

  

 

    [18]


 
[19]
[19][20]

[21]
et al.


[22] Likewise,



In spite of the low rate of virus isolation from tears sampling,
     
et al.


[23]

et al.

    

[24]

    
  


Mela et al.



[27]


  
et al. addressed
     

dosage, although over a relatively short period of time, that is

[28]
  
[29,30] Although there has


[31,32]
 
    
[33]
       
   

  



 

    
 

    




   




Conclusion
   
     
    

[Downloaded free from http://www.ijo.in on Wednesday, February 17, 2021, IP: 60.241.30.158]
694  Volume 69 Issue 3
  
     

  


 


Financial support and sponsorship

Conicts of interest

References
 

 




 




 et al


   
Amrane S, et al 
  
  

 




 

 et al
 
  

     
 


    
  


 



     et al


  
et al

  


   
et al

     
 



 


 
     
et al


 
et al

 

 
et al 

 et al
  


    



    

 

  

 

     
     

        



    
et al
 

 

 

  et al

  

 et al




   
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... Covid-19 has multiple ophthalmic manifestations, most common being conjunctivitis. [2,3] Few cases of orbital cellulitis have also been reported. Kumar et al. noted a case of orbital cellulitis with pansinusitis in an already COVID-positive patient. ...
... Kumar et al. noted a case of orbital cellulitis with pansinusitis in an already COVID-positive patient. [2] A case series elaborated nine patients with unilateral combined endophthalmitis and orbital cellulitis in COVID-19 patients. [4] Carvalho et al. also reported progression from pansinusitis to orbital cellulitis in a COVID-19 patient. ...
... [1] Demographic data are scarce, though in previous reports, both the subjects were above 50 years of age. [1,2] To the best of our knowledge, this is the third report of this specific entity published in medical literature. Necrotizing dacryometaplasia (ND) is a rare entity which can mimic an aggressive malignant tumor. ...
Article
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Coronavirus infection most commonly presents with mild influenza-like symptoms. The most common ocular presentation is conjunctivitis. We report four patients of COVID-19 infection presenting as orbital cellulitis. They all were incidentally found COVID-19 positive on reverse transcription polymerase chain reaction. All had painful edema of eyelids, extraocular movement restriction, and other symptoms of orbital cellulitis at presentation. Three of 4 had uncontrolled diabetes and one had coronary artery disease. Proven mucormycosis was present in two patients; cerebral involvement (abscess and stroke in 1 each) in two patients. Two of them died, one underwent orbital exenteration and one developed hemiplegia due to stroke. COVID can present as orbital cellulitis and carries a very grave prognosis.
... In addition, COVID-19 has also been found to have ophthalmic manifestations [1]. These include conjunctivitis, uveitis, retinal abnormalities, and other ocular manifestations [2,3]. Understanding the impact of COVID-19 on ophthalmology is crucial in providing safe and effective care to patients during this challenging time, which is the aim of this brief review. ...
Article
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Since its emergence in early 2020, the SARS-CoV-2 infection has had a significant impact on the entire eye care system. Ophthalmologists have been categorized as a high-risk group for contracting the virus due to the belief that the eye may be a site of inoculation and transmission of the SARS-CoV-2 infection. As a result, clinical ophthalmologists, optometrists, and eyecare professionals have had to familiarize themselves with the ocular manifestations of COVID-19, as well as its treatments and vaccines. The implementation of measures to prevent the transmission of the virus, such as restrictions, lockdowns, telemedicine, and artificial intelligence (AI), have led to substantial and potentially irreversible changes in routine clinical practice, education, and research. This has resulted in the emergence of a new mode of managing patients in a routine clinical setting. This brief review aims to provide an overview of various aspects of COVID-19 in ophthalmology, including the ocular manifestations related to the disease, the modes of transmission of SARS-CoV-2 infection, precautions taken in ophthalmic practice to prevent the spread of the virus, drugs, and vaccines used in the treatment of COVID-19, the impact of the pandemic on patients, clinicians, and the eye care system as a whole, and the future of ophthalmology conditioned by this global pandemic experience.
... Während der akuten Infektion schwanken die Prävalenzen für eine Augenbeteiligungen zwischen 2 % und 32 % [193][194][195][196][197][198]. Für eine Assoziation einer COVID-19 mit ophthalmologischen Befunden muss ein akuter bzw. ...
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Zusammenfassung Die Deutsche Gesellschaft für Pneumologie hat 2021 die AWMF S1-Leitlinie Long-/Post-COVID initiiert. In einem breiten interdisziplinären Ansatz wurde diese S1-Leitlinie basierend auf dem aktuellen Wissensstand gestaltet. Die klinische Empfehlung beschreibt die aktuellen Long- bzw. Post-COVID-Symptome, diagnostische Ansätze und Therapien. Neben der allgemeinen und konsentierten Einführung wurde ein fachspezifischer Zugang gewählt, der den aktuellen Wissensstand zusammenfasst. Die Leitlinie hat einen explizit praktischen Anspruch und wird basierend auf dem aktuellen Wissenszugewinn vom Autorenteam weiterentwickelt und adaptiert.
... Σε μελέτη από την Ινδία, μόνο ένας στους 2742 ασθενείς παρουσίασε κυτταρίτιδα κόγχου λόγω πανκολπίτιδας. 70 Σύμφωνα με άλλη μελέτη, έξι (1,4%) από τους 425 θετικούς στον SARS-CoV-2 ασθενείς ανέπτυξαν δευτεροπαθή μυκητιασική κυτταρίτιδα κόγχου. 68 Οι Shires et al. παρουσίασαν περίπτωση ασθενούς 76 ετών με υπέρταση, σακχαρώδη διαβήτη και παροδικό ισχαιμικό επεισόδιο που διαγνώστηκε με SARS-CoV-2 και στη συνέχεια ανέπτυξε ιγμορίτιδα, αποστήμα κόγχου και οστεομυελίτιδα. ...
Article
Three years after the onset of the SARS-CoV-2 pandemic, COVID-19 is still responsible for major morbidity in the general population, although mortality has declined significantly. Various systems and organs of the human body, including the eyes, have been reported to be affected by the disease. The virus attachement to ACE2 receptors on the ocular surface and conjunctiva of patients, transmission from upper respiratory infection via the nasolacrimal duct and bloodborne infection of the lacrimal glands are thought to be responsible for the ocular manifestations. Various forms of conjunctivitis, keratitis, episcleritis, vitreitis, optic papilledema, retinal disorders, such as central vein or artery occlusions, but also a number of neuro-ocular complications with oculomotor nerve palsies, angle-closure glaucoma and fungal infections such as mucormycosis have been described. The purpose of this review is to present , for the first time in the Greek literature , the various ocular manifestations of COVID-19, the thorough understanding of which is important in order to provide accurate treatment recommendations , prevent undesirable complications and improve the patients» quality of life.
... It has been hypothesized that Dr. Li Wenliang, a deceased ophthalmologist from Wuhan, China, caught the virus by ocular transmission [51]. Ocular symptoms occur in between 2% and 32% of patients with COVID-19 [52][53][54][55][56]. ...
Article
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Coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) in March 2020. It was caused by the highly pathogenic SARS-Cov-2 virus. Although the majority of its clinical manifestations are associated with airway involvement, extrapulmonary damage does occur in some situations. In light of the above discussion, this study of the literature tries to identify the ophthalmological disorders produced by infection with the new coronavirus. Although ocular symptoms do not correspond to the disease’s standard clinical presentation, there are reports of some ophthalmological alterations in COVID-19 individuals, the most prevalent of which is conjunctivitis.
... It has been hypothesized that Dr. Li Wenliang, a deceased ophthalmologist from Wuhan, China, caught the virus by ocular transmission [51]. Ocular symptoms occur in between 2% and 32% of patients with COVID-19 [52][53][54][55][56]. ...
Article
Objective: Our study aims to build on our understanding of COVID-19 by detailing a comprehensive look at the prevalence of different ocular manifestations related to COVID-19 infection. Design: This study is a systematic review and meta-analysis. Methods: Eligible studies published between June 20, 2021, and May 11, 2023, were retrieved from the MEDLINE, EMBASE, and CINAHL databases as well as grey literature. Covidence was used to conduct the systematic review. Duplicate records were removed, and 2 independent reviewers screened records for relevance. After screening, a risk-of-bias assessment was carried out. Data were extracted, and a meta-analysis was performed using STATA 14.0. Fixed-effects and random-effects models were computed based on heterogeneity. Results: Our meta-analysis included 43 articles with a total of 10,572 subjects. The results showed that COVID-19 patients had a significantly higher prevalence of conjunctivitis (effect size [ES] = 0.11; 95% CI, 0.07-0.15), ptosis (ES = 0.22; 95% CI, 0.15-0.30), and ophthalmoplegia (ES = 0.40; 95% CI, 0.06-0.74). Our results also indicate that COVID-19 patients have higher prevalence of cotton wool spots (ES = 0.06; 95% CI, 0.03-0.09), retinal hemorrhages (ES = 0.12; 95% CI, 0.06-0.18), and retinal vein tortuosity (ES = 0.19; 95% CI, 0.09-0.35). Conclusion: COVID-19 can exhibit extrapulmonary manifestations, affecting both the anterior and posterior segments of the eye. Common anterior-segment findings include conjunctivitis, whereas posterior-segment findings may include cotton wool spots, retinal hemorrhages, and retinal vein tortuosity. Improving our understanding of the ocular manifestations of COVID-19 has the potential to facilitate quicker diagnosis and subsequent treatment.
Article
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Necrotizing dacryometaplasia (ND) is a rare entity which can mimic an aggressive malignant tumor. It seems to be analogous to necrotizing sialometaplasia which generally affects the salivary glands and is an inflammatory condition. There is scarce information about this entity as only two case reports have been reported in the last two decades. Due to the presence of adjacent bony erosion, it may mimic an aggressive malignant tumor. Here, we report a 27-year-old male who presented with right upper eyelid swelling for 2 months, which clinically and radiologically pointed to be a malignancy turned out to be ND.
Article
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Apart from the systemic cardinal symptoms such as fever, cough, fatigue, headache, and diarrhea, ocular symptoms have gained much importance during the peak hours of the COVID pandemic. Since an exposed ocular surface can act as a gateway for various respiratory viruses, there is an increased interest in exploring the ocular route of transmission and viral RNA detection in ocular fluids. Moreover, the ocular surface can also share some common viral binding receptors. A large number of case reports and observational studies have been published so far reporting anterior, posterior, orbital, and neurological complications of the eye and orbit. Ocular complications can range from mild self-limiting pathologies such as conjunctivitis, episcleritis, and retinal cotton wool spots to severe blinding pathologies such as mucormycosis, retinal vessel occlusions, candida retinitis, and optic neuritis. There is an increased risk of corneal graft rejection and reactivation of certain microorganisms post severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccination. The present narrative review provides a brief overview of the current literature and an in-depth understanding of the ocular implications of SARS-CoV-2.
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Background: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, many studies have reported the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the conjunctival sac of patients infected with this virus, with several patients displaying symptoms of viral conjunctivitis. However, to our best knowledge, there is no in-depth report on the course of patients with COVID-19 complicated by relapsing viral conjunctivitis or keratoconjunctivitis. Case presentation: A 53-year-old man confirmed with COVID-19 developed symptoms of viral conjunctivitis in the left eye approximately 10 days after the onset of COVID-19. The results of a nucleic acid test were positive for SARS-CoV-2 in the conjunctival sac of the left eye. The symptoms were relieved 6 days after treatment. However, the patient was subsequently diagnosed with viral keratoconjunctivitis in both eyes 5 days after the symptoms in the left eye were satisfactorily relieved. The disease progressed rapidly, with spot staining observed at the periphery of the corneal epithelium. Although SARS-CoV-2 could not be detected in conjunctival secretions, the levels of inflammatory factors, such as interleukin-6, were increased in both eyes. Both eyes were treated with glucocorticoids, and symptoms were controlled within 5 days. There was no recurrence. Conclusions: In this case report, the pathogenesis, clinical manifestations, treatment, and outcome of a case with COVID-19 complicated by relapsing viral keratoconjunctivitis is described, and the involvement of topical cytokine surge in the pathogenesis of COVID-19 as it relates to viral keratoconjunctivitis is reported.
Article
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The proximity required of a thorough biomicroscopic slit-lamp examination may put ophthalmologists at increased risk for respiratory-borne infection with SARS-CoV-2. Conjunctivitis has been described in a few patients with COVID-19 and other coronavirus syndromes. Although SARS-CoV-2 has been detected in the conjunctival secretions or tears of patients with COVID-19 and conjunctivitis, transmission of infection through respiratory droplets to ophthalmologists without eye protection or masks may be the bigger concern.
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COVID-19 first presented in Wuhan, Hubei Province, China, in December 2019. Thought to be of zoonotic origin, it has been named SARS-CoV-2 (COVID-19) and has spread rapidly. As of April 20th, 2020, there have been more than 2.4 million cases recorded worldwide. The inflammatory process, cytokine storm, and lung injury that are associated with COVID-19 can put patients at an increased risk of thrombosis. It is uncertain what the total incidences of thrombotic events in COVID-19 patients is currently at. Those with more severe disease and with other risk factors, including increasing age, male sex, obesity, cancer, comorbidities, and intensive care unit admission, are at higher risk of these events. However, there is little international guidance on managing these risks in COVID-19 patients. In this paper, we explore the current evidence and theories surrounding thrombosis in these unique patients and reflect on experience from our center.
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SARS‐CoV‐2 is assumed to use angiotensin‐converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. Recent studies have described conjunctival congestion in 0.8% of patients with laboratory‐confirmed SARS‐CoV‐2, and there has been speculation that SARS‐CoV‐2 can be transmitted through the conjunctiva. However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctiva, 12 melanoma, 7 squamous cell carcinoma and 7 papilloma samples, were analyzed using high‐throughput RNA sequencing to assess mRNA expression of the SARS‐CoV‐2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP. ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. Our results show that the SARS‐CoV‐2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median 0.0 transcripts per million (TPM), min 0.0 TPM, max 1.7 TPM) and protein levels. Similar results were obtained for the transcription of other auxiliary molecules. In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS‐CoV‐2 via these mediators unlikely. This article is protected by copyright. All rights reserved.
Article
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The proposed doses of chloroquine (CQ) and hydroxychloroquine (HCQ) for treatment of COVID-19 (1000 mg/day for 10 days, CQ; 800 mg first day then 400 mg/day for 5 days, HCQ) in many guidelines worldwide, are considerably higher than the maximum recommended daily safe doses of both agents (≤2.3 mg/kg/day, CQ; ≤5.0 mg/kg/day, HCQ) for development of retinal toxicity. Irreversible retinal damage can occur if the exposure to the safe doses is >5 years. It is not known whether exposure to high doses over a short period of time can also cause the damage. We recommend that before prescribing CQ or HCQ, history of ocular disease should be obtained to avoid the prescription if appropriate. If either agent is to be used, routine baseline ocular examination is not absolutely necessary. Patients who do not have ocular disease should also be informed about the potential risk of retinal toxicity. Both agents, however, have not yet been proven to be beneficial to COVID-19.
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Objective The ongoing pandemic of coronavirus disease (COVID‐19), caused by the SARS‐CoV‐2 virus, is highly contagious with high morbidity and mortality. The role of the nasal and paranasal sinus cavities is increasingly recognized for COVID‐19 symptomatology and transmission. We therefore conducted a systematic review, synthesizing existing scientific evidence about sinonasal pathophysiology in COVID‐19. Study design Systematic review. Methods Systematic searches were performed of all indexed studies in PubMed/Medline and Cochrane databases through March 28, 2020 and studies searchable on preprints.com (including ArXiv and Scilit repositories) through March 30, 2020. Data extraction focused on sinonasal pathophysiology in COVID‐19. Results A total 19 studies were identified. The sinonasal cavity may be a major site of infection by SARS‐CoV‐2, where susceptibility genes required for infection are expressed at high levels and may be modulated by environmental and host factors. Viral shedding appears to be highest from the nose, therefore reflecting a major source for transmission. This has been highlighted by multiple reports of healthcare‐associated infection during rhinologic procedures, which are now consequently considered to be high risk for SARS‐CoV‐2 transmission to healthcare workers. While sinonasal symptomatology, such as rhinorrhea or congestion, appears to be a rarer symptom of COVID‐19, anosmia without nasal obstruction is reported as highly specific predictor of COVID‐19+ patients. Conclusion Sinonasal pathophysiology is increasingly important in our understanding of COVID‐19. The sinonasal tract may be an important site of infection while sinonasal viral shedding may be an important transmission mechanism—including healthcare‐associated infection. Anosmia without nasal obstruction may be a highly specific indicator of COVID‐19. This article is protected by copyright. All rights reserved.
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Objective To better inform efforts to treat and control the current outbreak with a comprehensive characterization of COVID-19. Methods We searched PubMed, EMBASE, Web of Science, and CNKI (Chinese Database) for studies published as of March 2, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I². Publication bias was assessed using Egger's test. Results 43 studies involving 3600 patients were included. Among COVID-19 patients, fever (83.3% [95% CI 78.4–87.7]), cough (60.3% [54.2–66.3]), and fatigue (38.0% [29.8–46.5]) were the most common clinical symptoms. The most common laboratory abnormalities were elevated C-reactive protein (68.6% [58.2–78.2]), decreased lymphocyte count (57.4% [44.8–69.5]) and increased lactate dehydrogenase (51.6% [31.4–71.6]). Ground-glass opacities (80.0% [67.3–90.4]) and bilateral pneumonia (73.2% [63.4–82.1]) were the most frequently reported findings on computed tomography. The overall estimated proportion of severe cases and case-fatality rate (CFR) was 25.6% (17.4–34.9) and 3.6% (1.1–7.2), respectively. CFR and laboratory abnormalities were higher in severe cases, patients from Wuhan, and older patients, but CFR did not differ by gender. Conclusions The majority of COVID-19 cases are symptomatic with a moderate CFR. Patients living in Wuhan, older patients, and those with medical comorbidities tend to have more severe clinical symptoms and higher CFR.
Article
Background In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19. Methods We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated with HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days) for at least three days. Outcomes were death, clinical worsening (transfer to ICU, and >10 day hospitalization) and viral shedding persistence (>10 days). Results A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years – range 14–95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74–95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective beta-blocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision). Conclusion Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with very low fatality rate in patients.
Chapter
Novel Coronavirus Disease (COVID-19) has become a rapidly growing pandemic involving several nations. It is of serious concern and extreme challenge not only to the health personnel but also to the countries for containment. The causative organism is SARS-CoV-2, RNA virus of subgenus Sarbecovirus, similar to the SARS virus, and seventh member of the human coronavirus family responsible for this zoonotic infection. It binds to the human angiotensin converting enzyme (hACE-2) receptor and causes constitutional and respiratory symptoms. The major mode of transmission is human to human and the median incubation period is 4 days. The most common symptom as studied from various cohorts of COVID-19 patients are fever (83–98%) followed by fatigue (70%) and dry cough (59%); gastrointestinal symptoms are relatively uncommon differentiating it from SARS and MERS. Most of the SAR-CoV-2 infection are mild (80%) with a usual recovery period of 2 weeks. COVID-19 commonly affects males in the middle age and elderly age group, with highest case fatality (8–15%) among those aged >80 years. The disease begins with fever, dry cough, fatigue and myalgia progressing to dyspnoea and ARDS over 6 and 8 days post exposure, respectively. Underlying co-morbidities increase mortality in COVID-19. Poor prognostic factors are elderly, co-morbidities, severe lymphopaenia, high CRP and D-dimer >1 μg/L. The overall mortality rate ranges from 1.5 to 3.6%. COVID-19 has to be differentiated from other viral and bacterial pneumonias as they are more common among healthy adults. Despite constant and vigorous efforts by researchers and health agencies, we are far from containment, cure or prevention by vaccine; hence right information and stringent prevention and control measures are the only weapon in the armoury to combat the ongoing infection.
Article
Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Findings Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Funding Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.