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1.
Nat Commun ; 13(1):2539, 2022.
Article in English | PubMed | ID: covidwho-1830055

ABSTRACT

Extrapulmonary complications of different organ systems have been increasingly recognized in patients with severe or chronic Coronavirus Disease 2019 (COVID-19). However, limited information on the skeletal complications of COVID-19 is known, even though inflammatory diseases of the respiratory tract have been known to perturb bone metabolism and cause pathological bone loss. In this study, we characterize the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bone metabolism in an established golden Syrian hamster model for COVID-19. SARS-CoV-2 causes significant multifocal loss of bone trabeculae in the long bones and lumbar vertebrae of all infected hamsters. Moreover, we show that the bone loss is associated with SARS-CoV-2-induced cytokine dysregulation, as the circulating pro-inflammatory cytokines not only upregulate osteoclastic differentiation in bone tissues, but also trigger an amplified pro-inflammatory cascade in the skeletal tissues to augment their pro-osteoclastogenesis effect. Our findings suggest that pathological bone loss may be a neglected complication which warrants more extensive investigations during the long-term follow-up of COVID-19 patients. The benefits of potential prophylactic and therapeutic interventions against pathological bone loss should be further evaluated.

2.
Cellular & Molecular Immunology ; 19(5):588-601, 2022.
Article in English | MEDLINE | ID: covidwho-1830046

ABSTRACT

Live attenuated vaccines might elicit mucosal and sterilizing immunity against SARS-CoV-2 that the existing mRNA, adenoviral vector and inactivated vaccines fail to induce. Here, we describe a candidate live attenuated vaccine strain of SARS-CoV-2 in which the NSP16 gene, which encodes 2'-O-methyltransferase, is catalytically disrupted by a point mutation. This virus, designated d16, was severely attenuated in hamsters and transgenic mice, causing only asymptomatic and nonpathogenic infection. A single dose of d16 administered intranasally resulted in sterilizing immunity in both the upper and lower respiratory tracts of hamsters, thus preventing viral spread in a contact-based transmission model. It also robustly stimulated humoral and cell-mediated immune responses, thus conferring full protection against lethal challenge with SARS-CoV-2 in a transgenic mouse model. The neutralizing antibodies elicited by d16 effectively cross-reacted with several SARS-CoV-2 variants. Secretory immunoglobulin A was detected in the blood and nasal wash of vaccinated mice. Our work provides proof-of-principle evidence for harnessing NSP16-deficient SARS-CoV-2 for the development of live attenuated vaccines and paves the way for further preclinical studies of d16 as a prototypic vaccine strain, to which new features might be introduced to improve safety, transmissibility, immunogenicity and efficacy.

4.
Nature Microbiology ; 27:27, 2022.
Article in English | MEDLINE | ID: covidwho-1815549

ABSTRACT

Emerging SARS-CoV-2 variants continue to cause waves of new infections globally. Developing effective antivirals against SARS-CoV-2 and its variants is an urgent task. The main protease (Mpro) of SARS-CoV-2 is an attractive drug target because of its central role in viral replication and its conservation among variants. We herein report a series of potent alpha-ketoamide-containing Mpro inhibitors obtained using the Ugi four-component reaction. The prioritized compound, Y180, showed an IC50 of 8.1 nM against SARS-CoV-2 Mpro and had oral bioavailability of 92.9%, 31.9% and 85.7% in mice, rats and dogs, respectively. Y180 protected against wild-type SARS-CoV-2, B.1.1.7 (Alpha), B.1.617.1 (Kappa) and P.3 (Theta), with EC50 of 11.4, 20.3, 34.4 and 23.7 nM, respectively. Oral treatment with Y180 displayed a remarkable antiviral potency and substantially ameliorated the virus-induced tissue damage in both nasal turbinate and lung of B.1.1.7-infected K18-human ACE2 (K18-hACE2) transgenic mice. Therapeutic treatment with Y180 improved the survival of mice from 0 to 44.4% (P = 0.0086) upon B.1.617.1 infection in the lethal infection model. Importantly, Y180 was also highly effective against the B.1.1.529 (Omicron) variant both in vitro and in vivo. Overall, our study provides a promising lead compound for oral drug development against SARS-CoV-2.

5.
JCI Insight ; 2022.
Article in English | PubMed | ID: covidwho-1807763

ABSTRACT

SARS-CoV-2 has resulted in over 450 million confirmed cases since 2019. Although several vaccines have been certified by World Health Organization and are being vaccinated on a global scale, it has been reported that multiple SARS-CoV-2 variants can escape neutralisation by antibodies, resulting in vaccine breakthrough infections. Bacillus Calmette-Guérin (BCG) is known to induce heterologous protection based on trained immune responses. Here, we investigated whether BCG-induced trained immunity protected against SARS-CoV-2 challenge in the K18-hACE2 mouse model. Our data demonstrates that intravenous BCG vaccination induces robust trained innate immune responses and provides protection against wild-type SARS-CoV-2 as well as the B.1.617.1 and B.1.617.2 variants. Further studies suggest that myeloid cell differentiation and activation of the glycolysis pathway are associated with BCG-induced training immunity in the K18-hACE2 mice. Overall, our study provides the experimental evidence that establishes a causal relationship between intravenous BCG vaccination and protection against SARS-CoV-2 challenge.

6.
Aids ; 2022.
Article in English | PubMed | ID: covidwho-1806746

ABSTRACT

OBJECTIVE: People living with HIV (PLHIV) co-infected with SARS-CoV-2 are at higher odds of severe diseases. Whereas the immunogenicity of mRNA vaccine and adenovirus-vectored vaccine was similar between PLHIV in stable condition and healthy adults, the effects of inactivated vaccines are not known. DESIGN: Prospective longitudinal observational study in real-world setting. METHODS: Adult PLHIV in care and planning to receive either inactivated (Day 0 and 28) or mRNA-based (Day 0 and Day 21) vaccine against SARS-CoV-2 were recruited, with blood samples collected over 6 months for surrogate virus neutralisation test (sVNT). Demographic and clinical data including age, gender, CD4 count, and suppressed viral load (SVL) status were transcribed for analyses, by simple and multivariable linear regression models, and multivariable linear generalised estimating equations (GEE). RESULTS: A total of 611 HIV patients, 91% male, were recruited, of whom 423 and 184 have received mRNA-based and inactivated vaccine respectively. The seroconversion rate was 99% for mRNA-based vs 86% for inactivated vaccine (OR = 21.56, p = 0.004). At 6 months, mRNA-based vaccine continued to give a higher response (94% vs 57%, p < 0.001). The temporal pattern varied between the 2 vaccines. By GEE, mRNA-based vaccine (B = 40.59, p < 0.001) and latest SVL status (B = 10.76, p = 0.01) were positively associated with sVNT level, but not latest CD4 count. CONCLUSIONS: In HIV patients, inactivated vaccine gave a lower peak and shorter duration of sVNT responses compared to mRNA vaccine. The results suggested that different strategies may be needed in boosting the immunity in anticipation of the emergence of variants in the community.

7.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333508

ABSTRACT

BACKGROUND: Serological tests are crucial tools for assessments of SARS-CoV-2 exposure, infection and potential immunity. Their appropriate use and interpretation require accurate assay performance data. METHOD: We conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV-2 antibodies. The specimen set comprised 128 plasma or serum samples from 79 symptomatic SARS-CoV-2 RT-PCR-positive individuals;108 pre-COVID-19 negative controls;and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with Coronavirus Disease 2019 (COVID-19). Samples were blinded and LFA results were interpreted by two independent readers, using a standardized intensity scoring system. RESULTS: Among specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8-100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3-100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.7-94.8%. No consistent cross-reactivity was observed. CONCLUSION: Our evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals. Informed use of serology will require evaluations covering the full spectrum of SARS-CoV-2 infections, from asymptomatic and mild infection to severe disease, and later convalescence. Well-designed studies to elucidate the mechanisms and serological correlates of protective immunity will be crucial to guide rational clinical and public health policies.

8.
Sci Transl Med ; : eabn6859, 2022.
Article in English | PubMed | ID: covidwho-1794534

ABSTRACT

The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well-conserved among sarbecoviruses, but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

9.
Gynecologic Oncology ; 164(1):28-29, 2022.
Article in English | EMBASE | ID: covidwho-1757942

ABSTRACT

Objectives: To investigate the delay in surgical management of abnormal uterine bleeding with endometrial sampling during the peak of the COVID-19 pandemic at a single, urban tertiary medical center. Methods: We conducted a retrospective chart review of 868 patients, 466 who received an endometrial biopsy in 2019 and 402 between January 1–March 23, 2020 (during the first peak of COVID-19) at a tertiary academic medical center in Philadelphia. We collected baseline patient characteristics including: age, self-identified race or ethnicity, and BMI. We assessed the time from an abnormal endometrial biopsy to surgical management, use of at least one telemedicine appointment between biopsy and surgical management, and resulting pathology results. Chi-squared test was used to compare proportions of populations and two-tailed student's T-test was used to compare days between biopsy and surgical management. P-value was set at 0.05. Results: 466 and 402 patients underwent an endometrial biopsy in 2019 and between January 1 – March 23, 2020, respectively. In 2019, 4.94% were diagnosed with an endometrial malignancy and 95.1% had resulting benign pathology;while in 2020, 5.22% had a diagnosed endometrial malignancy and 94.8% had benign pathology (p-value = 0.84). Median age was 51.0 years (range, 19.0–89.0) in 2019 and 51.0 years (range 24–89) in 2020. Median BMI was 31.4 (range, 17.6–66.9) in 2019 and 31.1 (range, 16.3–74.2) in 2020. Median time between endometrial biopsy and surgical management was 66.5 days (range, 0–453 days) in 2019 and 94.0 days (range 13.0–335) in 2020 (p-value = 0.57). Median time from biopsy to surgery for patients with a resulting pathology of endometrial malignancy was 53 days (range, 0–441) in 2019 and 87.5 days (range 13.0–323) in 2020 (p-value = 0.50). Median time for patients with resulting benign pathology was 69.0 days (range, 9.00–453) in 2019 and 112 days (range, 33.0–335) in 2020 (p-value = 0.48). 57.4% of patients in 2020 had at least one telemedicine appointment with their physician between the initial encounter for abnormal uterine bleeding and surgical treatment, while no patients had a telemedicine appointment in 2019. Conclusions: During the COVID-19 pandemic, individual patients with abnormal uterine bleeding may have experienced delays between initial abnormal endometrial biopsy and surgical management. However, comparing the populations as a whole, there was not a statistical difference in time between biopsy and surgical management for abnormal uterine bleeding, reinforcing the quality of care given to our patients. However, further studies are needed to examine the effects of COVID-19 on possible delay in surgical treatment from first symptoms in patients with abnormal uterine bleeding to biopsy and to surgical management.

10.
Western Journal of Emergency Medicine ; 23(1.1):S31, 2022.
Article in English | EMBASE | ID: covidwho-1743915

ABSTRACT

Learning Objectives: Assess the effectiveness of social media implementation of an Accreditation Council for Graduate Medical Education (ACGME) milestone-based curriculum during the spring 2020 US COVID-19 surge. The hypothesis is that pre-interns will report improvements in PP regarding multiple ACGME milestone topics. Background: Transitioning to residency involves translation of academic knowledge into clinical acumen, and is complicated by variable medical school experiences. The COVID-19 pandemic presented a new challenge by displacing students from clinical rotations. Virtual educational modalities such as the Slack Intern Curriculum (SIC) have increased newly-matched “pre-intern” perceived preparedness (PP) for residency in prior years, but the SIC had never been implemented or evaluated in a pandemic with disrupted medical education. Objective: Assess the effectiveness of social media implementation of an Accreditation Council for Graduate Medical Education (ACGME) milestone-based curriculum during the spring 2020 U.S. COVID-19 surge. The hypothesis is that pre-interns will report improvements in PP regarding multiple ACGME milestone topics. Methods: The SIC was constructed using topics from 8 ACGME milestones in emergency medicine (EM), incorporated into 8 clinical scenarios. Residency recruitment occurred via national EM listservs;of 276 programs, 27 enrolled. Curricular implementation was on Slack workspaces. Cases included stimulus images and clinical questions. Ample discussion time, answers, and resources were provided. Trends in PP were calculated with descriptive statistics and the Wilcoxon Rank Sum test. Results: Of 311 total pre-interns contacted, 289 (92.9%) completed a presurvey in April/May 2020, and 240 (77.2%) completed a post-survey in June/July 2020, for an 83.9% followthrough rate. Pre-interns reported statistically significant increases in PP both overall and regarding 14 of 21 milestones. See Table 1. Conclusions: Amidst the educational disruption of the COVID-19 pandemic, pre-interns participating in the SIC reported statistically significant increases in PP. Limitations include absence of control or pre-pandemic data. Future directions include adapting the SIC to other specialties' ACGME milestones for generalizability across all fields.

11.
MEDLINE; 2020.
Preprint in English | MEDLINE | ID: ppcovidwho-329976

ABSTRACT

COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) since 2012. Treatment options for CoVs are largely lacking. Here, we show that clofazimine, an anti-leprosy drug with a favorable safety and pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 replication in multiple in vitro systems, including the human embryonic stem cell-derived cardiomyocytes and ex vivo lung cultures. The FDA-approved molecule was found to inhibit multiple steps of viral replication, suggesting multiple underlying antiviral mechanisms. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and fecal viral shedding, and also prevented cytokine storm associated with viral infection. Additionally, clofazimine exhibited synergy when administered with remdesivir. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. Taken together, our data provide evidence that clofazimine may have a role in the control of the current pandemic SARS-CoV-2, endemic MERS-CoV in the Middle East, and, possibly most importantly, emerging CoVs of the future.

12.
Mult Scler J Exp Transl Clin ; 8(1): 20552173221078834, 2022.
Article in English | MEDLINE | ID: covidwho-1736272

ABSTRACT

Background: Susac Syndrome (SuS) is an autoimmune endotheliopathy impacting the brain, retina and cochlea that can clinically mimic multiple sclerosis (MS). Objective: To evaluate non-lesional white matter demyelination changes in SuS compared to MS and healthy controls (HC) using quantitative MRI. Methods: 3T MRI including myelin water imaging and diffusion basis spectrum imaging were acquired for 7 SuS, 10 MS and 10 HC participants. Non-lesional white matter was analyzed in the corpus callosum (CC) and normal appearing white matter (NAWM). Groups were compared using ANCOVA with Tukey correction. Results: SuS CC myelin water fraction (mean 0.092) was lower than MS(0.11, p = 0.01) and HC(0.11, p = 0.04). Another myelin marker, radial diffusivity, was increased in SuS CC(0.27µm2/ms) compared to HC(0.21µm2/ms, p = 0.008) and MS(0.23µm2/ms, p = 0.05). Fractional anisotropy was lower in SuS CC(0.82) than HC(0.86, p = 0.04). Fiber fraction (reflecting axons) did not differ from HC or MS. In NAWM, radial diffusivity and apparent diffusion coefficient were significantly increased in SuS compared to HC(p < 0.001 for both measures) and MS(p = 0.003, p < 0.001 respectively). Conclusions: Our results provided evidence of myelin damage in SuS, particularly in the CC, and more extensive microstructural injury in NAWM, supporting the hypothesis that there are widespread microstructural changes in SuS syndrome including diffuse demyelination.

13.
European Heart Journal ; 43(SUPPL 1):i225-i226, 2022.
Article in English | EMBASE | ID: covidwho-1722401

ABSTRACT

Background: Medical research is critical to professional advancement, and mentoring is an important means of early research engagement in medical training. In contrast to international research collaborations, research mentoring programs are often locally limited. With the COVID- 19 pandemic causing drifts to virtual classes and conferences, virtual international medical research mentoring may be viable. We hereby describe our experience with a virtual, international mentorship group for cardiovascular research. Methods: Our virtual international research mentorship group has been running since 2015. The group focuses on risk stratification and outcomes research in cardiovascular medicine and epidemiology. Mentees from any country or region in all stages of medical careers are welcomed. Considering the increasing emphasis of contemporary research on multidisciplinary healthcare and translational research, our team also includes allied healthcare professionals or students, and graduates from natural sciences (Figure 1). With our members' diverse backgrounds, we firmly adhere to the principle that all members must be given equal opportunities and treatment, regardless of their age, gender, race, nationality, sexual orientation, family background, and institution of study or practice. We make use of virtual platforms and multi-level mentoring (both senior and peer mentoring), and emphasize active participation, early leadership, open culture, accessible research support, and a distributed research workflow (i.e. an accessible-distributed model). Results: Since establishment, our group has expanded to include 63 active members from 14 countries (Figure 2), leading a total of 109 peer-reviewed original studies and reviews published. We observed no significant difficulty in communication between team members, nor conflicts due to differences in nationality or ethnicity. Most studies involve cross-country and ethnicity collaborations, and inter-disciplinary and inter-regional knowledge exchanges are frequent. Multi-level mentoring ensured mentoring quality without compromising bonding and communication. Conclusion: An accessible-distributed model of virtual international medical research collaboration and multi-level mentoring is viable, efficient, and caters to the needs of contemporary healthcare. We hope that others will build similar models and improve medical research mentoring globally. (Figure Presented).

14.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-327005

ABSTRACT

Highly transmissible SARS-CoV-2 Omicron variant has posted a new crisis for COVID-19 pandemic control. Within a month, Omicron is dominating over Delta variant in several countries probably due to immune evasion. It remains unclear whether vaccine-induced memory responses can be recalled by Omicron infection. Here, we investigated host immune responses in the first vaccine-breakthrough case of Omicron infection in Hong Kong. We found that the breakthrough infection rapidly recruited potent cross-reactive broad neutralizing antibodies (bNAbs) against current VOCs, including Alpha, Beta, Gamma, Delta and Omicron, from unmeasurable IC50 values to mean 1:2929 at around 9-12 days, which were higher than the mean peak IC50 values of BioNTech-vaccinees. Cross-reactive spike- and nucleocapsid-specific CD4 and CD8 T cell responses were detected. Similar results were also obtained in the second vaccine-breakthrough case of Omicron infection. Our preliminary findings may have timely implications to booster vaccine optimization and preventive strategies of pandemic control.

15.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326824

ABSTRACT

The Omicron (B.1.1.529) variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 (coronavirus disease 2019) vaccines and antibody therapies4. This concern is amplified by the findings from our study. We found B.1.1.529 to be markedly resistant to neutralization by serum not only from convalescent patients, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 17 of the 19 antibodies tested were either abolished or impaired, including ones currently authorized or approved for use in patients. In addition, we also identified four new spike mutations (S371L, N440K, G446S, and Q493R) that confer greater antibody resistance to B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.

16.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326792

ABSTRACT

The devastation caused by SARS-CoV-2 has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses and thus its promise as an agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses, but also uncovered a new antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

19.
Gastroenterology ; 160(6):S-900-S-901, 2021.
Article in English | EMBASE | ID: covidwho-1597689

ABSTRACT

Background: COVID-19's precise impact on cancer patients and their oncologic care providers remains poorly understood. This study aims at comparatively analyzing COVID-19's effect on cancer care from both a patient and provider perspective. METHODS: A multi-institutional survey was developed to assess COVID-19 specific concerns regarding treatment, safety, and emotional stress through 5-point Likert type prompts and open-ended questions before and after start of the pandemic. Wilcoxon signed-rank and -rank-sum tests were used to analyze before/after answers for providers and patients independently. Open-ended responses were assessed using inductive thematic analysis. RESULTS: The survey was completed by 104 (69.3%) patients and 50 (50%) providers. Patients demonstrated significant change in only 1 of 15 Likert prompts. Most significant were increased concern regarding susceptibility to infection [z=2.536, p=0.011] and concerns regarding their cancer outcome [z=4.572, p<0.001]. Non-physician providers demonstrated significant change in 8 of 13 Likert prompts, whereas physicians had all 13 Likert prompts change in the COVID-19 setting. Physicians believed care to be more poorly planned [z=-3.857, p=<0.001], availability of protective personal equipment (PPE) to be more limited [z=-4.082, p<0.001], and were significantly concerned infecting family members [z=4.965, p<0.001]. CONCLUSION: While patients had more difficulty coping with their cancer, they did not perceive significant differences in their actual treatment. This suggests the need for a renewed focus on patients' coping with cancer. Among providers, physicians more than any other provider group had a strong negative perception of COVID-19's impact on healthcare, suggesting the need for novel approaches to target physician burnout. (Table presented.)

20.
Respirology ; 26(SUPPL 3):19, 2021.
Article in English | EMBASE | ID: covidwho-1583441

ABSTRACT

Background and Aims: The North Lantau Hospital Hong Kong Infection Control Centre (HKICC) was established in February 2021 as a designated hospital to combat the coronavirus disease 2019 (COVID-19) in Hong Kong, during which an increase in emergent mutant strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raised concerns pertinent to increased transmissibility and disease severity. We aim to describe the treatment outcomes of SARS-CoV-2 infection in HKICC, and to evaluate the impact of mutant strains in imported cases. Methods: Consecutive patients with COVID-19 admitted to HKICC from February to April 2021 were identified with their clinical features and treatment outcomes evaluated. Clinical features of mutant strains and wild-type strains were compared. Results: of 513 COVID-19 patients treated in HKICC (mean age 38 years, 45.2% male), 238 (46.4 %) were imported. The incidence of hypoxemia was 3.1% (16/513). All patients were discharged successfully with a median length of stay of 10 days (IQR 6-13). All mutant strains were imported with an incidence of 47.9% (114/238), N501Y mutation was most frequently found (111/114, 97.4%). Among imported cases, strains with N501Y mutation alone were associated with more cough (16.5% vs 6.5%, p=0.022), but had similar incidence of hypoxemia and length of stay, compared with wild-type strains. Conclusion: HKICC successfully contributed to combating COVID-19 pandemic in Hong Kong. Imported cases with N501Y mutation alone presented with more cough, but had similar incidence of hypoxemia and length of stay, compared with wild-type strains. Further studies to evaluate the impact of other mutant strains are warranted.

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