Comparative analysis of symptom profile and risk of death associated with infection by SARS-CoV-2 and its variants in Hong Kong.

The recurrent multiwave nature of coronavirus disease 2019 (COVID-19) necessitates updating its symptomatology. We characterize the effect of variants on symptom presentation, identify the symptoms predictive and protective of death, and quantify the effect of vaccination on symptom development. With the COVID-19 cases reported up to August 25, 2022 in Hong Kong, an iterative multitier text-matching algorithm was developed to identify symptoms from free text. Multivariate regression was used to measure associations between variants, symptom development, death, and vaccination status. A least absolute shrinkage and selection operator technique was used to identify a parsimonious set of symptoms jointly associated with death. Overall, 70.9% (54 450/76 762) of cases were symptomatic with 102 symptoms identified. Intrinsically, the wild-type and delta variant caused similar symptoms among unvaccinated symptomatic cases, whereas the wild-type and omicron BA.2 subvariant had heterogeneous patterns, with seven symptoms (fatigue, fever, chest pain, runny nose, sputum production, nausea/vomiting, and sore throat) more frequent in the BA.2 cohort. With ≥2 vaccine doses, BA.2 was more likely than delta to cause fever among symptomatic cases. Fever, blocked nose, pneumonia, and shortness of breath remained jointly predictive of death among unvaccinated symptomatic elderly in the wild-type-to-omicron transition. Number of vaccine doses required for reducing occurrence varied by symptoms. We substantiate that omicron has a different clinical presentation compared to previous variants. Syndromic surveillance can be bettered with reduced reliance on symptom-based case identification, increased weighing on symptoms predictive of death in outcome prediction, individual-based risk assessment in care homes, and incorporating free-text symptom reporting.

Transmission of monkeypox/mpox virus: A narrative review of environmental, viral, host, and population factors in relation to the 2022 international outbreak.

Monkeypox virus (MPXV) has spread globally. Emerging studies have now provided evidence regarding MPXV transmission, that can inform rational evidence-based policies and reduce misinformation on this topic. We aimed to review the evidence on transmission of the virus. Real-world studies have isolated viable viruses from high-touch surfaces for as long as 15 days. Strong evidence suggests that the current circulating monkeypox (mpox) has evolved from previous outbreaks outside of Africa, but it is yet unknown whether these mutations may lead to an inherently increased infectivity of the virus. Strong evidence also suggests that the main route of current MPXV transmission is sexual; through either close contact or directly, with detection of culturable virus in saliva, nasopharynx, and sperm for prolonged periods and the presence of rashes mainly in genital areas. The milder clinical presentations and the potential presence of presymptomatic transmission in the current circulating variant compared to previous clades, as well as the dominance of spread amongst men who have sex with men (MSMs) suggests that mpox has a developed distinct clinical phenotype that has increased its transmissibility. Increased public awareness of MPXV transmission modalities may lead to earlier detection of the spillover of new cases into other groups.

Airborne transmission of respiratory viruses including severe acute respiratory syndrome coronavirus 2.

PURPOSE OF REVIEW: The coronavirus disease 2019 pandemic has had a wide-ranging and profound impact on how we think about the transmission of respiratory viruses This review outlines the basis on which we should consider all respiratory viruses as aerosol-transmissible infections, in order to improve our control of these pathogens in both healthcare and community settings. RECENT FINDINGS: We present recent studies to support the aerosol transmission of severe acute respiratory syndrome coronavirus 2, and some older studies to demonstrate the aerosol transmissibility of other, more familiar seasonal respiratory viruses. SUMMARY: Current knowledge on how these respiratory viruses are transmitted, and the way we control their spread, is changing. We need to embrace these changes to improve the care of patients in hospitals and care homes including others who are vulnerable to severe disease in community settings.

Prospective Surveillance of Respiratory Infections in British Antarctic Survey Bases During the COVID-19 Pandemic.

BACKGROUND: The British Antarctic bases offer a semiclosed environment for assessing the transmission and persistence of seasonal respiratory viruses. METHODS: Weekly swabbing was performed for respiratory pathogen surveillance (including SARS-CoV-2), at 2 British Antarctic Survey bases, during 2020: King Edward Point (KEP, 30 June to 29 September, 9 participants, 124 swabs) and Rothera (9 May to 6 June, 27 participants, 127 swabs). Symptom questionnaires were collected for any newly symptomatic cases that presented during this weekly swabbing period. RESULTS: At KEP, swabs tested positive for non-SARS-CoV-2 seasonal coronavirus (2), adenovirus (1), parainfluenza 3 (1), and respiratory syncytial virus B (1). At Rothera, swabs tested positive for non-SARS-CoV-2 seasonal coronavirus (3), adenovirus (2), parainfluenza 4 (1), and human metapneumovirus (1). All bacterial agents identified were considered to be colonizers and not pathogenic. CONCLUSIONS: At KEP, the timeline indicated that the parainfluenza 3 and adenovirus infections could have been linked to some of the symptomatic cases that presented. For the other viruses, the only other possible sources were the visiting ship crew members. At Rothera, the single symptomatic case presented too early for this to be linked to the subsequent viral detections, and the only other possible source could have been a single nonparticipating staff member.

Rhinovirus persistence during the COVID-19 pandemic-Impact on pediatric acute wheezing presentations.

Rhinoviruses have persisted throughout the COVID-19 pandemic, despite other seasonal respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, adenoviruses, human metapneumovirus) being mostly suppressed by pandemic restrictions, such as masking and other forms of social distancing, especially during the national lockdown periods. Rhinoviruses, as nonenveloped viruses, are known to transmit effectively via the airborne and fomite route, which has allowed infection among children and adults to continue despite pandemic restrictions. Rhinoviruses are also known to cause and exacerbate acute wheezing episodes in children predisposed to this condition. Noninfectious causes such as air pollutants (PM2.5 , PM10 ) can also play a role. In this retrospective ecological study, we demonstrate the correlation between UK national sentinel rhinovirus surveillance, the level of airborne particulates, and the changing patterns of pediatric emergency department presentations for acute wheezing, before and during the COVID-19 pandemic (2018-2021) in a large UK teaching hospital.

Hypothesis: All respiratory viruses (including SARS-CoV-2) are aerosol-transmitted.

The potential role of aerosol transmission for seasonal respiratory viruses has been dramatically highlighted during the ongoing COVID-19 pandemic. It is now evident that short-range (conversational) and long-range aerosol transmission plays at least some part in how all these respiratory viruses are transmitted between people. This article highlights and discusses various studies that form the basis for this hypothesis.

What were the historical reasons for the resistance to recognizing airborne transmission during the COVID-19 pandemic?

The question of whether SARS-CoV-2 is mainly transmitted by droplets or aerosols has been highly controversial. We sought to explain this controversy through a historical analysis of transmission research in other diseases. For most of human history, the dominant paradigm was that many diseases were carried by the air, often over long distances and in a phantasmagorical way. This miasmatic paradigm was challenged in the mid to late 19th century with the rise of germ theory, and as diseases such as cholera, puerperal fever, and malaria were found to actually transmit in other ways. Motivated by his views on the importance of contact/droplet infection, and the resistance he encountered from the remaining influence of miasma theory, prominent public health official Charles Chapin in 1910 helped initiate a successful paradigm shift, deeming airborne transmission most unlikely. This new paradigm became dominant. However, the lack of understanding of aerosols led to systematic errors in the interpretation of research evidence on transmission pathways. For the next five decades, airborne transmission was considered of negligible or minor importance for all major respiratory diseases, until a demonstration of airborne transmission of tuberculosis (which had been mistakenly thought to be transmitted by droplets) in 1962. The contact/droplet paradigm remained dominant, and only a few diseases were widely accepted as airborne before COVID-19: those that were clearly transmitted to people not in the same room. The acceleration of interdisciplinary research inspired by the COVID-19 pandemic has shown that airborne transmission is a major mode of transmission for this disease, and is likely to be significant for many respiratory infectious diseases.

Convalescent Plasma Therapy for COVID-19: State of the Art.

Convalescent plasma (CP) therapy has been used since the early 1900s to treat emerging infectious diseases; its efficacy was later associated with the evidence that polyclonal neutralizing antibodies can reduce the duration of viremia. Recent large outbreaks of viral diseases for which effective antivirals or vaccines are still lacking has renewed the interest in CP as a life-saving treatment. The ongoing COVID-19 pandemic has led to the scaling up of CP therapy to unprecedented levels. Compared with historical usage, pathogen reduction technologies have now added an extra layer of safety to the use of CP, and new manufacturing approaches are being explored. This review summarizes historical settings of application, with a focus on betacoronaviruses, and surveys current approaches for donor selection and CP collection, pooling technologies, pathogen inactivation systems, and banking of CP. We additionally list the ongoing registered clinical trials for CP throughout the world and discuss the trial results published thus far.

A Paradigm Shift to Align Transmission Routes With Mechanisms.

Current infection-control guidelines subscribe to a contact/droplet/airborne paradigm that is based on outdated understanding. Here, we propose to modify and align existing guidelines with a more accurate description of the different transmission routes. This will improve the effectiveness of control measures as more transmissible variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge.

Psychobehavioral Responses and Likelihood of Receiving COVID-19 Vaccines during the Pandemic, Hong Kong.

To access temporal changes in psychobehavioral responses to the coronavirus disease (COVID-19) pandemic, we conducted a 5-round (R1-R5) longitudinal population-based online survey in Hong Kong during January-September 2020. Most respondents reported wearing masks (R1 99.0% to R5 99.8%) and performing hand hygiene (R1 95.8% to R5 97.7%). Perceived COVID-19 severity decreased significantly, from 97.4% (R1) to 77.2% (R5), but perceived self-susceptibility remained high (87.2%-92.8%). Female sex and anxiety were associated with greater adoption of social distancing. Intention to receive COVID-19 vaccines decreased significantly (R4 48.7% to R5 37.6%). Greater anxiety, confidence in vaccine, and collective responsibility and weaker complacency were associated with higher tendency to receive COVID-19 vaccines. Although its generalizability should be assumed with caution, this study helps to formulate health communication strategies and foretells the initial low uptake rate of COVID-19 vaccines, suggesting that social distancing should be maintained in the medium term.

Retrospective SARS-CoV-2 IgG screening during the first wave (March-June 2020) of the COVID-19 pandemic in the United Kingdom.

During the "first wave" of the coronavirus disease 2019 (COVID-19) pandemic in the United Kingdom (March-June 2020), the city of Leicester was particularly hard hit, resulting in reimposed lockdown measures. Although initial polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was attempted within the community, testing was soon abandoned due to an inability to keep up with demand by local laboratories. It is therefore feasible that undiagnosed transmission of COVID-19 in the community by asymptomatic individuals was a real possibility. Therefore, retrospective SARS-CoV-2 immunoglobulin G (IgG) testing of archived sera from out-patients visiting University Hospitals of Leicester NHS Trust service was performed to investigate the transmission of SARS-CoV-2 in the community. A total of 1779 sera samples were tested from samples collected between 16th March and 3rd June 2020, of which 202 (11.35%) were SARS-CoV-2 IgG positive. Positivity was lowest in March (2.54%) at the beginning of the pandemic before peaking in April (17.16%) before a decline in May and June (11.16% and 12.68%, respectively). This retrospective screening offers some insight into the early patterns of SARS-CoV-2 transmission within a sampled community population during the first wave of the COVID-19 pandemic; supporting the argument for more community screening during high incidences of pandemics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroconversion in hematology-oncology patients.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, the virus has spread rapidly across the globe leading to millions of infections and subsequent deaths. Although the virus infects those exposed indiscriminately, there are groups in society at an increased risk of severe infection, leading to increased morbidity. Patients suffering from hematological cancers, particularly leukemia, lymphoma, and myeloma, may be one such group and previous studies have suggested that they may be at a three to four times greater risk of severe COVID-19 after SARS-CoV-2 infection, leading to admissions to ICU, mechanical ventilation, and death compared to those without such malignancies. Serological testing for IgG seroconversion has been extensively studied in the immunocompetent, but fewer publications have characterized this process in large series of immunocompromised patients. This study described 20 patients with hematological cancers who tested positive for SARS-CoV-2 via PCR with 12 of the patients receiving further serological testing. We found that of the 12 patients screened for SARS-CoV-2 IgG antibodies, only 2 (16.6%) were able to generate an immune response to the infection. Yet despite this low seroconversion rate in this cohort, none of these patients died or became particularly unwell with COVID-19 or its related complications.

Xpert Xpress Flu/RSV: Validation and impact evaluation at a large UK hospital trust.

Despite vaccination programs and antivirals, influenza remains a prominent cause of morbidity and mortality. The Xpert Xpress Flu/respiratory syncytial virus (RSV) test is a leading influenza point-of-care test, but its evaluation has been limited to nasopharyngeal samples. In addition, the clinical impacts of Xpress Flu/RSV have not yet been quantified. We evaluated the performance of Xpress Flu/RSV at three locations in a UK Hospital Trust against an existing laboratory assay. Multiple upper respiratory tract sample types were included. In addition, we calculated time saved by Xpert, and the associations between Xpert use and rates of early patient isolation and antiviral prescription as recorded at the time of the laboratory result being telephoned out. A total of 642 patients were included in the diagnostic performance analysis. There were 177 laboratory-confirmed cases of influenza A, 7 influenza B and 86 RSV. For influenza A, sensitivity and specificity were 96.6% (95% confidence interval [CI]: 92.8%-98.8%) and 98.1% (CI: 96.4%-99.1%), respectively. This was sustained across all locations and sample types. The negative predictive value was 98.7% (CI: 97.2%-99.4%). The median amount of time saved was 27.1 h. Xpert use was associated with sixfold higher rates of isolation and threefold higher rates of antiviral prescribing by the time the laboratory result was available. Sensitivity for RSV was lower at 86.0% (95% CI: 76.9%-92.6%). Xpert Xpress Flu/RSV reliably detects influenza A infection and has significant clinical impacts. Cartridge optimization is required to enable accurate multiplexing, including from a range of sample types.

An outbreak of adenovirus D8 keratoconjunctivitis in Leicester, United Kingdom, from March to August 2019.

We report a large epidemic (n = 126) of keratoconjunctivitis predominantly with two lineages of adenovirus (AdV) type D8 in patients seen in eye casualty between march and August 2019. Other AdV species identified by viral sequencing included B, C, and E. Despite various features of more severe eye disease being present, these were not significantly different between the different AdV species, with similar rates of pseudomembrane formation and keratitis observed in patients with AdV species B as for those with AdV species D.

Clinical performance of Roche cobas 6800, Luminex ARIES, MiRXES Fortitude Kit 2.1, Altona RealStar, and Applied Biosystems TaqPath for SARS-CoV-2 detection in nasopharyngeal swabs.

We compared the performance of five assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection on nasopharyngeal swab samples: Roche "cobas," Luminex "ARIES," MiRXES "Fortitude," Altona "RealStar," and Thermo Fisher Scientific "TaqPath." A total of 94 nasopharyngeal swab samples were obtained from 80 confirmed coronavirus disease 2019 cases in the first 2 weeks of illness (median, 7 days; range, 2-14 days) and 14 healthy controls. After collection, all samples were transported to the hospital clinical laboratory within 24 h. These samples were tested on all five assays within 3 days of sample receipt. Of the 94 samples, 69 yielded the same result on all platforms, resulting in an agreement of 73.4% (69 of 94). Of these, 14 were the healthy control swabs which all tested negative, demonstrating good specificity across all platforms. The ARIES assay had the lowest detection rate (68.8%), followed by Fortitude (85.0%), RealStar (86.3%), cobas (95.0%), and TaqPath (100%). Statistically significant differences were observed for ARIES, Fortitude, and RealStar when compared against the best performing TaqPath using McNemar's χ2 test. A consensus result was established based on the results obtained by the cobas, Fortitude, RealStar, and TaqPath. Six discrepancies had failed to reach a consensus and were adjudicated using the Cepheid Xpert Xpress SARS-CoV-2. Overall, the TaqPath and cobas assays were the most sensitive at detecting their designated SARS-CoV-2 gene targets. On the other hand, the ARIES assay was the least sensitive, thus warranting the need for assay re-optimization before go-live at the testing laboratory.

Lethal zoonotic coronavirus infections of humans - comparative phylogenetics, epidemiology, transmission, and clinical features of coronavirus disease 2019, The Middle East respiratory syndrome and severe acute respiratory syndrome.

PURPOSE OF REVIEW: Severe acute respiratory syndrome-coronaviruses-2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged as a new zoonotic pathogen of humans at the end of 2019 and rapidly developed into a global pandemic. Over 106 million COVID-19 cases including 2.3 million deaths have been reported to the WHO as of February 9, 2021. This review examines the epidemiology, transmission, clinical features, and phylogenetics of three lethal zoonotic coronavirus infections of humans: SARS-CoV-1, SARS-CoV-2, and The Middle East respiratory syndrome coronavirus (MERS-COV). RECENT FINDINGS: Bats appear to be the common natural source of SARS-like CoV including SARS-CoV-1 but their role in SARS-CoV-2 and MERS-CoV remains unclear. Civet cats and dromedary camels are the intermediary animal sources for SARS-CoV-1 and MERS-CoV infection, respectively whereas that of SARS-CoV-2 remains unclear. SARS-CoV-2 viral loads peak early on days 2-4 of symptom onset and thus high transmission occurs in the community, and asymptomatic and presymptomatic transmission occurs commonly. Nosocomial outbreaks are hallmarks of SARS-CoV-1 and MERS-CoV infections whereas these are less common in COVID-19. Several COVID-19 vaccines are now available. SUMMARY: Of the three lethal zoonotic coronavirus infections of humans, SARS-CoV-2 has caused a devastating global pandemic with over a million deaths. The emergence of genetic variants, such as D614G, N501Y (variants 1 and 2), has led to an increase in transmissibility and raises concern about the possibility of re-infection and impaired vaccine response. Continued global surveillance is essential for both SARS-CoV-2 and MERS-CoV, to monitor changing epidemiology due to viral variants.

Susceptibility of an Airborne Common Cold Virus to Relative Humidity.

The viability of airborne respiratory viruses varies with ambient relative humidity (RH). Numerous contrasting reports spanning several viruses have failed to identify the mechanism underlying this dependence. We hypothesized that an "efflorescence/deliquescence divergent infectivity" (EDDI) model accurately predicts the RH-dependent survival of airborne human rhinovirus-16 (HRV-16). We measured the efflorescence and deliquescence RH (RHE and RHD, respectively) of aerosols nebulized from a protein-enriched saline carrier fluid simulating the human respiratory fluid and found the RH range of the aerosols' hygroscopic hysteresis zone (RHE-D) to be 38-68%, which encompasses the preferred RH for indoor air (40-60%). The carrier fluid containing HRV-16 was nebulized into the sub-hysteresis zone (RHD) air, to set the aerosols to the effloresced/solid or deliquesced/liquid state before transitioning the RH into the intermediate hysteresis zone. The surviving fractions (SFs) of the virus were then measured 15 min post nebulization. SFs were also measured for aerosols introduced directly into the RHD zones without transition. SFs for transitioned aerosols in the hysteresis zone were higher for effloresced (0.17 ± 0.02) than for deliquesced (0.005 ± 0.005) aerosols. SFs for nontransitioned aerosols in the RHD zones were 0.18 ± 0.06, 0.05 ± 0.02, and 0.20 ± 0.05, respectively, revealing a V-shaped SF/RH dependence. The EDDI model's prediction of enhanced survival in the hysteresis zone for effloresced carrier aerosols was confirmed.

The need for improved discharge criteria for hospitalised patients with COVID-19-implications for patients in long-term care facilities.

In the COVID-19 pandemic, patients who are older and residents of long-term care facilities (LTCF) are at greatest risk of worse clinical outcomes. We reviewed discharge criteria for hospitalised COVID-19 patients from 10 countries with the highest incidence of COVID-19 cases as of 26 July 2020. Five countries (Brazil, Mexico, Peru, Chile and Iran) had no discharge criteria; the remaining five (USA, India, Russia, South Africa and the UK) had discharge guidelines with large inter-country variability. India and Russia recommend discharge for a clinically recovered patient with two negative reverse transcription polymerase chain reaction (RT-PCR) tests 24 h apart; the USA offers either a symptom based strategy-clinical recovery and 10 days after symptom onset, or the same test-based strategy. The UK suggests that patients can be discharged when patients have clinically recovered; South Africa recommends discharge 14 days after symptom onset if clinically stable. We recommend a unified, simpler discharge criteria, based on current studies which suggest that most SARS-CoV-2 loses its infectivity by 10 days post-symptom onset. In asymptomatic cases, this can be taken as 10 days after the first positive PCR result. Additional days of isolation beyond this should be left to the discretion of individual clinician. This represents a practical compromise between unnecessarily prolonged admissions and returning highly infectious patients back to their care facilities, and is of particular importance in older patients discharged to LTCFs, residents of which may be at greatest risk of transmission and worse clinical outcomes.

Correlating indoor and outdoor temperature and humidity in a sample of buildings in tropical climates.

The incidence of several respiratory viral infections has been shown to be related to climate. Because humans spend most of their time indoors, measures of indoor climate, rather than outdoor climate, may be better predictors of disease incidence and transmission. Therefore, understanding the relationship between indoor and outdoor climate will help illuminate their influence on the seasonality of diseases caused by respiratory viruses. Indoor-outdoor relationships between temperature and humidity have been documented in temperate regions, but little information is available for tropical regions, where seasonal patterns of respiratory viral diseases differ. We have examined indoor-outdoor correlations of temperature, relative humidity (RH), and absolute humidity (AH) over a 1-year period in each of seven tropical cities. Across all cities, the average monthly indoor temperature was 25 ± 3°C (mean ± standard deviation) with a range of 20-30°C. The average monthly indoor RH was 66 ± 9% with a range of 50-78%, and the average monthly indoor AH was 15 ± 3 g/m3 with a range of 10-23 g/m3 . Indoor AH and RH were linearly correlated with outdoor AH when the air conditioning (AC) was off, suggesting that outdoor AH may be a good proxy of indoor humidity in the absence of AC. All indoor measurements were more strongly correlated with outdoor measurements as distance from the equator increased. Such correlations were weaker during the wet season, especially when AC was in operation. These correlations will provide insight for assessing the seasonality of respiratory viral infections using outdoor climate data, which is more widely available than indoor data, even though transmission of these diseases mainly occurs indoors.

COVID-19 multisystem inflammatory syndrome in three teenagers with confirmed SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is generally a relatively mild illness in children. An emerging disease entity coined as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) has been reported recently, but is very rare and only affects a very small minority of children. Here we describe the clinical presentations and outcomes of three teenagers with serologically-confirmed SARS-CoV-2 infection admitted to a pediatric intensive care unit for PIMS-TS. Although their initial presentations were very similar, their COVID-19-related disease varied in severity.