COVID, Volume 2, Issue 3 (March 2022) – 15 articles

This study describes the implementation and utility of a standalone device designed, developed, and 3D-printed by PwC Singapore and Southeast Asia Consulting as a response to Corona Virus Disease 2019 (COVID-19), in the Emergency Department (ED) of the National University Hospital in Singapore. Over a 2-week period, all staff used the devices for the duration of their shifts, with the device additionally tagged to patients who were swabbed on suspicion of or surveillance for COVID-19 in the subsequent two weeks. Additional control hardware was placed in the ED to analyze (1) time-intervals of greatest interaction, (2) clusters of close physical distance among staff, (3) areas with high traffic, and (4) potential use of a rapid contact tracing capability. Time-day trends indicated the greatest interaction time-intervals during the beginning of the day, with Monday hosting the greatest average daily interactions across the first two weeks. Social cluster trends indicated the greatest average daily interactions between nurses–nurses during Phase 1, and patients–patients during Phase 2. User-location trends revealed the greatest average daily interaction counts at the intermediate care areas, isolation outdoor tent, pantry, and isolation holding units relative to other areas. Individual-level visualization and contact tracing capabilities were not utilized as nobody contracted COVID-19 during either phase. While congregation in intermediate and resuscitation areas are unavoidable within the ED context, the findings of this study were acted upon, improving social distancing within the pantry and between healthcare groups. This real-time solution addresses multiple privacy concerns while rapidly facilitating contact tracing. Full article

Despite extensive worldwide vaccination, the current COVID-19 pandemic caused by SARS-CoV-2 continues. The Omicron variant is a recently emerged variant of concern and is now overtaking the Delta variant. To characterize the potential antigenicity of the Omicron variant, we examined the distributions of SARS-CoV-2 nonself mutations (in reference to the human proteome) as five amino acid stretches of short constituent sequences (SCSs) in the Omicron and Delta proteomes. The number of nonself SCSs did not differ much throughout the Omicron, Delta, and reference sequence (RefSeq) proteomes but markedly increased in the receptor binding domain (RBD) of the Omicron spike protein compared to those of the Delta and RefSeq proteins. In contrast, the number of nonself SCSs decreased in non-RBD regions in the Omicron spike protein, compensating for the increase in the RBD. Several nonself SCSs were tandemly present in the RBD of the Omicron spike protein, likely as a result of selection for higher binding affinity to the ACE2 receptor (and, hence, higher infectivity and transmissibility) at the expense of increased antigenicity. Taken together, the present results suggest that the Omicron variant has evolved to have higher antigenicity and less virulence in humans despite increased infectivity and transmissibility. Full article

Background: Statins have a pleiotropic effect in addition to a lipid-lowering effect. Several studies have demonstrated that statins may reduce the mortality and severity of infectious diseases, such as pneumonia or sepsis. We investigated the protective effects of various statins on the coronavirus disease 2019 (COVID-19) using a population-based cohort covering the entire Korean population. Methods: Consecutive patients diagnosed with COVID-19 between January 2020 and May 2020 were enrolled from the Korean National Health Insurance Service database. Current statin users were defined as patients who used statins within 30 days before the diagnosis of COVID-19. We compared the mortality and severity of COVID-19 between statin users and non-users to confirm the efficacy of statins. Results: Of the 7723 patients with COVID-19 who were enrolled, 255 died due to COVID-19 and 493 had severe COVID-19 (defined as mortality, admission to the intensive care unit, or mechanical ventilator use). Compared with non-users, atorvastatin users had a lower risk of COVID-19 mortality (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.34–0.86) and severe COVID-19 (OR, 0.65; 95% CI, 0.45–0.93). However, other statins did not reduce the COVID-19 mortality and severity. Conclusions: Among the statins, only atorvastatin was effective in reducing the COVID-19 mortality and severity. Further randomized controlled trials are required to clarify the protective effects of atorvastatin. Full article

Direct optical detection methods such as surface plasmon resonance imaging (SPRi) and photonic-integrated-circuits (PIC)-based biosensors provide a fast label-free detection of COVID-19 antibodies in real-time. Each technology, i.e., SPRi and PIC, has advantages and disadvantages in terms of throughput, miniaturization, multiplexing, system integration, and cost-effective mass production. However, both technologies share similarities in terms of sensing mechanism and both can be used as high-content diagnostics at or near to point of care, where the analyte is not just quantified but comprehensively characterized. This is significant because recent results suggest that not only the antibody concentration of the three isotypes IgM, IgG, and IgA but also the strength of binding (affinity) gives an indication of potential COVID-19 severity. COVID-19 patients with high titers of low affinity antibodies are associated with disease severity. In this perspective, we provide some insights into how SPR and PIC technologies can be effectively combined and complementarily used for a comprehensive COVID-19 severity monitoring. This opens a route toward an immediate therapy decision to provide patients a treatment in an early stage of the infection, which could drastically lowers the risk of a severe disease course. Full article

The COVID-19 pandemic changed birth hospitalization, with many hospitals implementing restrictions. Little is known about the impact of the COVID-19 pandemic on rates of early newborn discharge and length of stay (LOS). The primary objective was to compare rates of early discharge before and after the start of the COVID-19 pandemic. Secondary objectives included 28-day readmissions and LOS. A single-center retrospective cohort study was undertaken of all live newborns discharged from a well newborn nursery in the United States between 1 July 2015 and 18 June 2021. The pre-COVID-19 era was defined as 1 July 2015 to 29 February 2020, and the COVID-19 era as 1 March 2020 to 18 June 2021, based on the first case reported in our state. Early discharge was defined as less than or equal to 24 h. A total of 10,589 newborns were included: 8094 before and 2495 after the COVID-19 pandemic started. Overall, 43 newborns (0.41%) were discharged early. In the COVID-19 era, early discharges significantly increased from 0.23% (n = 19) to 0.96% (n = 24) (p < 0.001). Median LOS declined from 52.0 (IQR, 43.0–64.0) to 45.0 (IQR, 37.0–56.0) hours (p < 0.001). The 28-day readmission rate decreased from 2.3% (n = 182) to 1.3% (n = 33) (p < 0.01). Since the start of the COVID-19 pandemic, the number of early discharges has significantly increased at our institution without an increase in readmissions. Additionally, overall decrease in length of stay for the birth hospitalization was observed. Potential reasons include changes in hospital unit policies including visitor limitations to reduce COVID-19 infection risk to patients and staff and/or parental concern for iatrogenic acquisition of the virus. Full article

Coronavirus Disease 2019 (COVID-19) has spread across the world, caused lockdowns, and has had serious economic and social consequences. COVID-19 manifests differently in children than adults, as children usually have a milder course of disease, mild symptoms if any, and lower fatality rates are recorded among children. SARS-CoV-2 transmission also seems to be different between children and adults. Many factors are proposed to explain the milder outcome in children, e.g., a more appropriate immune response (especially active innate response), trained immunity, a lack of immunosenescence, and the reduced prevalence of comorbidities. A better understanding of the differences in susceptibility and outcome in children compared with adults could lead to greater knowledge of risk factors for complicated COVID-19 cases and potential treatment targets. We highlight proposed reasons as to why children are less affected by COVID-19 than adults. Full article

The Coronavirus Disease 2019 (COVID-19) is a world-wide health crisis on a scale that has not been witnessed in modern times. Socio-economic (SE) factors impact every facet of human existence, including lifestyle, which significantly affects health-related quality of life. This article compiles major studies and discusses health disparities based on SE and community status in cardiovascular and cancer patients with a special focus on cardio-oncology in the context of COVID-19. Full article

Since the onset of the COVID-19 pandemic, four SARS-CoV-2 variants of concern have emerged, which have shifted the clinical and epidemiological characteristics of the disease. Of concern is the impact of the emerging variants on COVID-19 vaccination programmes, with vaccination perceived as a key global pandemic control strategy. Variants of concern can reduce the effectiveness of the currently available vaccines, shift herd immunity thresholds, and promote wider vaccine inequities as richer countries hoard vaccines for booster shots for their populations without accounting for the needs of the underdeveloped countries of sub-Saharan Africa. Currently, Africa lags far behind the rest of the world, with most sub-Saharan Africa countries still to reach 50% vaccination of their eligible populations against global herd immunity thresholds of 70–90%. As long as the vaccination gap between sub-Saharan Africa and the rest of the world persists, SARS-CoV-2 will most likely persist as a significant global health threat, with continued emergence of variants of concern. Therefore, strategies to ensure wider reach of different types of vaccines on the African continent are urgently required alongside fighting vaccine hesitancy and logistical barriers to access for the marginalized populations. Sub-Saharan Africa must look for opportunities to manufacture vaccines on the continent and enhance genomic sequencing capacity as key pandemic-control strategies. Full article

A systematic review of the literature investigating the effects of the COVID-19 pandemic on psychological and psychosocial factors was completed. Published literature was examined using electronic databases to search psychosocial factors such as beliefs and media persuasion, social support, coping, risk perception, and compliance and social distancing; and psychological factors as anxiety, stress, depression, and other consequences of COVID-19 that impacted mental health among the pandemic. A total of 294 papers referring to the first wave of the COVID-19 pandemic (December 2019–June 2020) were selected for the review. The findings suggested a general deterioration of mental health, delineating a sort of “psychological COVID-19 syndrome”, characterized by increased anxiety, stress, and depression, and decreased well-being and sleep quality. The COVID-19 effect on the psychological dimensions of interest was not the same for everyone. Indeed, some socio-demographic variables exacerbated mental health repercussions that occurred due to the pandemic. In particular, healthcare workers and young women (especially those in postpartum condition) with low income and low levels of education have been shown to be the least resilient to the consequences of the pandemic. Full article

Objective: This study investigated emotional distress and associated factors among the general population in the aftermath of the COVID-19 lockdown in China. Design and sample: An online nationwide survey was conducted using a self-designed questionnaire, which included items related to demography, lifestyle, and experience of emotional distress during the previous month of the pandemic period. A total of 10,545 respondents completed the survey. Results: Over 30% of participants reported experiencing one or more symptoms of emotional distress to a moderate or higher degree. Increased emotional distress was associated with COVID-19-related impact on diet (β = −1.106, 95% CI: −1.187 to −1.026, p < 0.001), experiencing food shortage (β = 1.334, 95% CI: 1.117 to 1.551, p < 0.001), lack of physical exercise (β = −0.845, 95% CI: −1.024 to −0.667, p < 0.001), younger age (β = −0.050, 95% CI: −0.062 to −0.039, p < 0.001), being a smoker (β = 0.852, 95% CI: 0.604 to 1.100, p < 0.001), lower education level (β = −0.524, 95% CI: −0.702 to −0.346, p < 0.001), and lack of medical insurance (β = −0.742, 95% CI: −1.012 to −0.473, p < 0.001). Emotional distress was negatively associated time spent sleeping (β = −0.020, 95% CI: −0.027 to −0.013, p < 0.001). Conclusion: The levels of emotional distress are high in the aftermath of the lockdown and associated with a number of demographic and lifestyle factors. Full article

Following COVID-19 exposure, the Centers for Disease Control (CDC) recommends a 10–14-day quarantine for asymptomatic individuals and more recently a 7-day quarantine with a negative PCR test. A university-based prospective cohort study to determine if early polymerase chain reaction (PCR) negativity predicts day 14 negativity was performed. A total of 741 asymptomatic students in quarantine was screened and 101 enrolled. Nasopharyngeal swabs were tested on days 3 or 4, 5, 7, 10, and 14, and the proportion of concordant negative results for each day versus day 14 with a two-sided 95% exact binomial confidence interval was determined. Rates of concordant negative test results were as follows: day 5 vs. day 14 = 45/50 (90%, 95% CI: 78–97%); day 7 vs. day 14 = 47/52 (90%, 95% CI: 79–97%); day 10 vs. day 14 = 48/53 (91%, 95% CI:79–97%), with no evidence of different negative rates between earlier days and day 14 by McNemar’s test, p > 0.05. Overall, 14 of 90 (16%, 95% CI: 9–25%) tested positive while in quarantine, with seven initial positive tests on day 3 or 4, 5 on day 5, 2 on day 7, and none on day 10 or 14. Based on concordance rates between day 7 and 14, we anticipate that 90% (range: 79–97%) of individuals who are negative on day 7 will remain negative on day 14, providing the first direct evidence that exposed asymptomatic students ages 18–44 years in a university setting are at low risk if released from quarantine at 7 days if they have a negative PCR test prior to release. In addition, the 16% positive rate supports the ongoing need to quarantine close contacts of COVID-19 cases. Full article

Coronavirus disease 2019 (COVID-19) is associated with fatal acute respiratory distress syndrome, which can be ameliorated by methylprednisolone pulse therapy, thereby reducing the risk of progression to respiratory failure and death. We aimed to determine the efficacy and safety of methylprednisolone pulse therapy for patients with COVID-19 pneumonia. In this retrospective, observational cohort study, seventy patients (age, 35–91 years) who were admitted to Saitama Medical University Hospital in Japan between March 2020 and January 2021 due to COVID-19 pneumonia were included. The difference in mortality between the methylprednisolone pulse therapy (n = 22) and dexamethasone therapy (n = 48) groups was the primary outcome. Between-group differences in the average length of intensive care unit stay, duration of invasive mechanical ventilation, and incidence of treatment-related adverse events were the secondary outcomes. The methylprednisolone pulse therapy group showed a significantly lower mortality rate (3.8% vs. 20.2%, p = 0.006) and increased survival rate compared with the dexamethasone therapy group (p = 0.044). Additionally, without statistical significance, the average length of intensive care unit stay tended to be shorter in the methylprednisolone pulse therapy group (11.5 ± 6.1 days) than in the dexamethasone therapy group (22.3 ± 23.1 days) (p = 0.793). The average duration of invasive mechanical ventilation also tended to be shorter in the methylprednisolone pulse therapy group (15.3 ± 10.1 vs. 28.8 ± 9.2 days, p = 0.120). There were no significant differences in the incidence of treatment-related serious adverse events between the two groups. In conclusion, methylprednisolone pulse therapy for patients with COVID-19 pneumonia significantly reduced mortality and increased the survival rate compared to conventional dexamethasone therapy. Full article

In this in silico study, different pharmaceutical co-crystals based on (hydroxy)chloroquine with macrolide antibiotics (azithromycin, clarithromycin, or erythromycin A) were analyzed for the first time. These findings present a new molecular perspective and therefore suggest that the combination of (hydroxy)chloroquine/azithromycin, in the stoichiometric ratio of 1:1, as model co-crystal systems has less toxicity and is the most effective for inhibiting the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Full article

The temporal evolution of the omicron wave in different countries is predicted, upon adopting an early doubling time of three days for the rate of new infections with this mutant. The forecast is based on the susceptible–infectious–recovered/removed (SIR) epidemic compartment model with a constant stationary ratio $k=\mu \left(t\right)/a\left(t\right)$ between the infection ($a\left(t\right)$) and recovery ($\mu \left(t\right)$) rates. The assumed fixed early doubling time then uniquely relates the initial infection rate $a_0$ to the ratio k; this way the full temporal evolution of the omicron wave is determined here. Three scenarios (optimistic, pessimistic, intermediate) and the resulting pandemic parameters are considered for 12 different countries. Parameters include the total number of infected persons, the maximum rate of new infections, the peak time and the maximum 7-day incidence per 100,000 persons. The monitored data from Great Britain underwent a clear maximum SDI of 1865 on 7 January 2022. This maximum is a factor 5.0 smaller than our predicted value in the optimistic case and may indicate a dark number of omicron infections of 5.0 in Great Britain. For Germany we predict peak times of the omicron wave ranging from 32 to 38 and 45 days after the start of the omicron wave in the optimistic, intermediate and pessimistic scenario, respectively, with corresponding maximum SDI values of 7090, 13,263 and 28,911. Adopting 1 January 2022 as the starting date our predictions imply the maximum of the omicron wave to be reached between 1 February and 15 February 2022. Rather similar values are predicted for Switzerland. Due to an order of magnitude smaller omicron hospitalization rate, in concert with a high percentage of vaccinated and boosted population, the German health system can cope with a maximum omicron SDI value of 2800 which is about a factor 2.5 smaller than the corresponding value 7090 for the optimistic case. By either reducing the duration of intensive care during peak time, and/or by making use of the nonuniform spread of the omicron wave across Germany, it seems that the German health system can barely cope with the omicron wave and thus avoid triage decisions. The reduced omicron hospitalization rate also causes significantly smaller mortality rates compared to the earlier mutants in Germany. Within the optimistic scenario, we predict 7445 fatalities and a maximum number of 418 deaths/day due to omicron. These numbers range in order of magnitude below the ones known from the beta mutant. Full article

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Several variants of concern (VOCs) have been identified so far. Recently, the B.1.1.529 (Omicron) variant of SARS-CoV-2 spread rapidly worldwide. We describe the first case of the Omicron genetic lineage BA.1 in our region. The patient is a physician who traveled to Johannesburg (South Africa) and returned to Reggio Calabria (Italy). He underwent a SARS-CoV-2 screening before leaving—a required procedure where travelers present a negative PCR test one-day prior to departing. Three days after arriving in Italy, he started experiencing cold symptoms. Clinically, he was without fever or severe respiratory symptoms and reported suffering from a cold and sore throat. The nasopharyngeal swab specimen was tested by TaqPath COVID-19 RT-PCR and sequenced by Sanger sequencing, and next-generation sequencing (NGS) data were processed with their relative software. A peculiar drop-off of the S gene was obtained with TaqPath COVID-19 RT-PCR. S gene mutations indicative of the Omicron variant were obtained with both sequencing methods, pointing out 17 mutations in the 29 recognized by Sanger and the 28 recognized by NGS. Full article