The coronavirus disease 2019 (COVID-19) pandemic has influenced current infection control practices in the healthcare setting. We surveyed 74 hospitals in Japan regarding changes in their infection control practices or policies between 2020 and the present. We found that the current hospital infection control practices for COVID-19 are adequate. Despite the importance of preventive measures against nosocomial transmission of SARS-CoV-2, the optimal SARS-CoV-2 infection control practices for acute-care hospitals are still moot. Some unresolved infection control–related issues remain, including what the indications for testing are, when patients should be quarantined, what constitutes appropriate personal protective equipment (PPE), when isolation precaution should be discontinued, what precautions should be taken in high flow nasal cannula (HFNC) use, and how infection control practices vary by institutions. We investigated the current infection control practices at the participating institutions and compare the most current infection control practices (February–April 2021) with those of February–April 2020.Since its inception in early 2020, the coronavirus disease 2019 (COVID-19) pandemic has posed significant challenges to infection control practices in various regions around the world. COVID-19 among healthcare workers (HCWs) and hospitalized patients has led to substantial increases in morbidity and mortality. Meanwhile, several new guidelines on infection control practices focusing on severe acute respiratory coronavirus virus 2 (SARS-CoV-2) have been hurriedly issued by professional societies.The current study was based on responses to a survey regarding infection control practices against SARS-CoV-2 which was sent to Japanese tertiary-care hospitals. The survey asked about hospital characteristics , individual-level practice , and hospital-level practice  during February–April 2020 and February–April 2021. This survey was reviewed by the other primary investigators (K.O. and H.S.) for finalization. The questionnaire was then distributed to participants  at hospitals caring for COVID-19 patients with a snowball sampling. The survey was conducted using Google forms from April 19, 2021, through May 16, 2021. The institutional review board at Tokyo Metropolitan Tama Medical Center approved the project.A draft of the questionnaire was developed by the primary investigators (H.H. and A.T.) based on the current infection control guidelines as well as our own clinical experience of COVID-19 infection control practice.During the study period, 74 hospitals responded to the survey. Table For PPE use, the N95 mask only or in combination with a surgical mask with an integrated eye shield was commonly used in both 2020 and 2021. The usage rate for each type of PPE did not change significantly between 2020 and 2021. Hair covers were commonly used, whereas shoe covers were not  and 1 year later (February–April 2021). The results revealed no significant change at the individual level  but indicated significant changes in hospital-level practices between the periods. However, significant variation was observed in the routine use of hair covers and shoe covers, which theoretically protect healthcare workers’ hair, scalp, and shoes from contamination by droplets, aerosols, and fomites. Covering the hair and shoes might be important for full protection, given the ability of SARS-CoV-2 to survive for days on surfaces. However, none of the current guidelines specifically address the use of these covers in routine practice. Given the high transmissibility of the virus, the efficacy of these coverings in COVID-19 care warrant further investigation in a real clinical setting.Although the mode of transmission of SARS-CoV-2, via either droplet or airborne route has been debated, the use of the N95 mask or its equivalent is now considered a standard precaution at many of the hospitals surveyed. Moreover, wearing full PPE, including a long-sleeved isolation gown and some form of eye protection, appeared to be commonplace, thanks to the recommendations of the current guidelines on PPE use. However, because either respiratory device can increase the risk of exposure to the virus and can contribute to its nosocomial spread, implementing a specific policy for HFNC and NPPV use is imperative from the infection control perspective.In 2021, with increasing use of HFNC and NPPV for patients with COVID-19, many hospitals implemented infection control protocols for their use. HFNC appears to be preferred presumably because of its ease of use and possible lower aerosol production.Progress in infection control practices in matters related to COVID-19 patient care also occurred in 2021. Increased availability of physical and occupational therapy, introduction of ultraviolet light devices for terminal room decontamination, and newly implemented online video devices for family meetings to enable greater contact between patients hospitalized with COVID-19 and their relatives reflect significant advances in the quality of infection control practices and patient/family care as well as responses specific to the exigencies of treating large numbers of elderly patients with COVID-19 in Japan.This study had some limitations. Although the questionnaire was addressed to hospitals in various areas of Japan, two-thirds of the participating centers were in Tokyo (Kanto), which may indicate sampling bias. The influence of variations in infection control practices on the incidence of nosocomial transmission of SARS-CoV-2 was not assessed. Since the survey was conducted between April and May 2021, the present study did not assess the impact of vaccinating HCW or the emergence of new variants  on infection control practices.In conclusion, whereas standard PPE use was already established in February–April 2020, hospital-level infection control practices against SARS-CoV-2 changed markedly between 2020 and 2021. Advances in hospital-level infection control measures were likely driven by the needs or demands of inpatient care. Although the ideal strategies for infection control practice are still moot, the findings of the present study ensure the current infection control practices and improved hospital safety culture for HCWs over the year.


A 44-year-old male with a history of deep venous thrombosis (DVT) and pulmonary embolism (PE) with the inferior vena cava (IVC) filter in place and peripheral vascular disease (PVD) status post lower extremity vascular stenting presented from a COVID-19 rehabilitation center with bilateral phlegmasia cerulea dolens and no palpable popliteal or dorsalis pedis pulses, at risk for venous gangrene and loss of limbs. The patient was anticoagulated and taken emergently to the operating room for vascular surgery where thrombolysis with alteplase and mechanical thrombectomy were performed. Bilateral thrombolysis infusion catheters were placed for two days. The patient had a return of arterial signals in the feet and decreasing clot burden. The patient is expected to make a full recovery.  COVID-19 has been widely studied since its outbreak in Wuhan, China, in December 2019. As of December 16, 2022, there have been more than 647 million confirmed cases of COVID-19 and more than six million deaths [Eighty-one percent of patients with COVID-19 have mild symptoms (no symptoms or mild pneumonia), 14% of patients have severe disease , and 5% of patients have a critical disease  . The mosMany patients with COVID-19 have an elevated D-dimer and are hypercoagulable, thought to result from endothelial injury . Venous A case report recently documented a 12-year-old girl who had tested positive for SARS-CoV-2 and presented with phlegmasia cerulea dolens with venous gangrene complicated by massive pulmonary embolism (PE) requiring emergent mechanical thrombectomy and extracorporeal membrane oxygenation . With thA 44-year-old male with a past medical history significant for ulcerative colitis status post colectomy, PE/deep vein thrombosis (DVT) with inferior vena cava (IVC) filter placement a few years prior, peripheral arterial disease (PAD) treated with lower extremity vascular stenting, newly diagnosed diabetes mellitus, and COVID-19 (IgG antibody positive) presented from a COVID-19 rehabilitation center for evaluation of worsening shortness of breath, abdominal pain, back pain, and left lower extremity pain. The patient stated that he had worsening shortness of breath for the past few days but woke up the morning of the presentation with abdominal pain, sciatic back pain, and excruciating left lower extremity pain. He reported that he had no sensation in his left lower extremity distal to the knee. At presentation, the patient had a heart rate of 145 beats per minute, respiratory rate of 26 breaths per minute, saturation of 99% on 15 L/minute of oxygen via a non-rebreather mask, blood pressure of 88/42 mmHg, and an oral temperature of 36.7 °C. On examination, the patient had edema and mottling of the bilateral lower extremities, left greater than right  device and sheath were passed from the left leg into the central venous circulation. The device was engaged and performed thrombolysis on the left with its functional element residing in the distal IVC adjacent to the filter . The device was withdrawn, and the wire was then passed up the right leg into the distal central circulation and 5 mg alteplase was infused. The device was withdrawn with its wires left in place. The alteplase was left to dwell in the distal IVC for 12 minutes. The device was then introduced first on the left and then on the right in thrombectomy mode and dissolved clots were suctioned. Cragg-McNamara™  catheters were then placed bilaterally, and the infusing tips were left adjacent to the IVC filter in the distal vena cava. The patient was transferred to the medical intensive care unit with ongoing bilateral thrombolysis. After the procedure, the patient had patent common iliac and external iliac veins bilaterally, with a moderate burden of thrombus surrounding the IVC filter in the mid-to-distal IVC. After the procedure, the patient had a return of arterial signals to the foot. On postoperation day (POD)-1, the patient had repeat venograms, which showed improvement of thrombus burden, but residual thrombus was present at the distal IVC and iliac bifurcation. The patient underwent catheter removal on POD-2. The patient has remained hemodynamically stable through his hospital course, has regained sensation in the lower extremity, and is expected to make a full recovery. inflammation; cerulea is from cerulean, which in Latin means dark blue; and dolens comes from Latin and denotes suffering. Therefore, in combination, phlegmasia cerulea dolens describes a painful discoloration that comes from inflammation. The tissue ischemia results from inflammation, causing increased interstitial pressure in the limb [Phlegmasia is derived from Greek for the limb . This cathe limb  or, worsthe limb .The aforementioned case demonstrates one of the many complications of COVID-19. Numerous studies have shown an increase in thromboembolic events in patients who have tested positive for COVID-19 -5,9. AddSometimes, a D-dimer level can be helpful to demonstrate hypercoagulability in the setting of COVID-19. Several case reports have documented thrombosis in the setting of COVID-19 and a positive D-dimer ,12. In oThe patient in this case report had a history of DVT/PE with an IVC filter and bilateral vascular stenting; whether anticoagulation would have prevented this severe complication of COVID-19 infection is uncertain. Amid the COVID-19 pandemic, clinicians must be aware of thrombotic complications of the disease and should consider anticoagulation in high-risk patients.Hypercoagulability is an increasingly common complication among COVID-19 patients. There is limited data on the utility of prophylactic and therapeutic anticoagulation in these patients, but it is important to consider its use in high-risk patients. Phlegmasia cerulea dolens is a rare complication, and clinicians should keep this on their differential when evaluating a patient suspected of having COVID-19.


The impact of the Coronavirus Disease-2019 (COVID-19) pandemic on pregnancy is not well-understood. During the outbreak, the initial approach suggested by the major societies was to postpone all non-urgent assisted reproductive technology (ART) treatments. Nevertheless, the Italian Society of Fertility and Sterility and Reproductive Medicine considered ethically correct to proceed with ART treatments, as the infertility rate is increasing over time, with a consistent decline in the live birth rate. The objective of our study was to assess the impact of the COVID-19 pandemic on the outcomes of ART pregnancies, in terms of early pregnancy loss, overall success rate, and live birth rate.n = 749) and from 1 March 2019 to 29 February 2020  were enrolled. The study had a duration of 24 months. Patients underwent baseline severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) nasopharyngeal swab; quantitative serum beta human chorionic gonadotropin (β-hCG) to assess pregnancy; pelvic transvaginal ultrasound; and follow-up until delivery. The study took place at the ART Center of the University Hospital in Florence, Italy.We conducted a single-center retro-prospective cohort study. Patients who underwent ART treatments from 1 March 2020 to 28 February 2021 , clinical pregnancy rate , and ectopic pregnancy rate . Neither first trimester miscarriage rate was different between the groups  nor second trimester miscarriage rate . Live birth rate remained unchanged during the pandemic  and stable even when compared to our center rate between 2015 and 2019 .There were not statistically significant differences on implantation rate (pART 0.348 ± 0.034 vs. CTR 0.365 ± 0.033, CI = 95%, The COVID-19 pandemic did not cause a statistically significant change in the live birth rate and in the pregnancy loss rate. ART during the COVID-19 pandemic can be considered fair and safe, ethically and medically appropriate. Patients and physicians should be reassured that ART pregnancy outcomes do not seem to be jeopardized by the pandemic state. Coronavirus Disease-2019 (COVID-19) is a respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). It was first described in December 2019 in Wuhan, China, has since spread globally, and has been declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The COVID-19 outbreak has medical implications that extend beyond the diagnosed patients, resulting in a ripple effect on every aspect of human life and disrupted social and economic function worldwide .This policy affects other fields in women's health, such as the treatment of infertility. During the outbreak, the initial approach suggested by the major societies was to postpone all non-urgent assisted reproductive technology (ART) treatments. On 19 March 2020, the European Society for Human Reproduction and Embryology (ESHRE) suggested preventing the establishment of new pregnancies through deferred embryo transfer, avoiding patients from traveling for fertility treatments, and decreasing additional stress on healthcare systems . SimilarThe approach of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) has been different. As infertility is increasing over time, simultaneously with a constant decline in the live birth rate, it was considered ethically correct to allow infertile couples to maintain a viable chance of a future pregnancy . In accoTo date, the impact of the COVID-19 pandemic on pregnancy, and specifically ART pregnancies, is not well-understood. In our study, we aimed to assess the impact of the pandemic on pregnancy outcomes in women who underwent ART treatments. To this aim, we compared, in women with positive pregnancy tests, pregnancy outcomes before and after the outbreak of the COVID-19 pandemic and investigated whether there was an adverse effect in terms of pregnancy loss and overall success rate.We conducted a retro-prospective cohort study at the ART Center of the tertiary maternal and Child Health Careggi University Hospital in Florence, Italy. The study population included subjects who underwent embryo transfer after gonadotropin stimulation (as part of either a fresh cycle or an exogenous hormone-supported frozen embryo transfer) or intrauterine insemination (IUI). In total, 749 subjects were enrolled in the study between March 2020 and February 2021 and were included in the pandemic ART (pART) cohort. As a control (CTR) cohort, we considered all patients (eight-hundreds and forty-four) who were referred to the same center between March 2019 and February 2020.in vitro fertilization (IVF) cycles in which day-3 embryos or blastocysts were obtained together with adequate endometrial preparation that allowed embryo transfer. The final phase of the fertility treatments was selected to minimize the variability and to create homogeneous groups (as many of the confounding associated with infertility decrease the probability to achieve embryos).We included in our study only the All patients had a quantitative serum beta human chorionic gonadotropin (β-hCG) level performed 11 days after blastocyst transfer or 13 days after day-3 embryo transfer. A pregnancy test was defined as positive if serum β-hCG levels >10 mIU/ml. A pelvic transvaginal ultrasound was performed in our center 2 weeks after a positive pregnancy test.We established COVID-free protocols for the safety of the patients and the medical personnel.Before each appointment in our center, all patients were given a triage questionnaire for COVID-19 symptoms and risk factors.All patients underwent a SARS-Cov-2 nasopharyngeal swab 48 h prior to ovarian pick-up, frozen embryo transfer, or IUI.If tested positive for COVID-19, the embryo transfer was postponed. Ovarian pick-up, however, was performed with oocyte cryopreservation in case of COVID-19 positivity the same day.We promoted the COVID-19 vaccination and prioritized the completion of the vaccination cycle before starting the ART treatments.Pregnancy was documented as a viable clinical pregnancy when an embryo with a fetal heart rate was present. Spontaneous abortion was defined as a non-viable, intrauterine pregnancy with either an empty gestational sac (blighted ovum) or a gestational sac containing an embryo or fetus without fetal heart activity. We distinguished early (within the first 12 + 6 weeks of gestation) and second-trimester spontaneous abortion (between 13 + 0 and 20 + 6 weeks of gestation). Stillbirth was defined as the delivery of a fetus showing no signs of life after 20 + 6 weeks.A biochemical pregnancy loss was determined in cases of a transient rise in serum β-hCG and was excluded from the clinical pregnancies amount. An ectopic pregnancy was documented in the presence of an extra-uterine gestational sac with a β-hCG level above the threshold for ultrasound visibility, with no evidence of an intrauterine pregnancy.After the confirmation of the pregnancy viability, an intensive follow-up was conducted until delivery. All pregnancy ultrasound scans, routine prenatal analysis, birth data, and neonatal outcomes were examined. The follow-up was performed remotely to minimize interpersonal interaction. During the follow-up, we also investigated whether the patient tested positive for COVID-19 during the pregnancy.We therefore compared the live birth rate during the pandemic to our Center overall live birth rate in the previous 5 years (2015–2019).U-test for non-parametric data. The data distribution was evaluated using the Shapiro-Wilk test in continuous variables. Continuous variables were represented using mean, standard deviation (SD), and median values, while categorical ones used absolute and relative frequencies and their 95% confidence interval (CI). Categorical data were compared using the χ2 test. A p-value of ≤ 0.05 was considered statistically significant.The statistical analyses were conducted using the statistical software package JMP version 15.2.0 . To assess whether the pART cohort and the CTR cohort are homogeneous, we used Fisher's exact test for binomial data and the Mann-Whitney The pART cohort and the CTR cohort were homogeneous in the variables that have been examined: maternal age, body mass index, type of infertility, and the use of oocytes or sperm donation .n = 294, 39.2%), male infertility , female and male infertility , and unexplained infertility . Similar distribution of the type of infertility was found among CTR cohort . Specifically, in the pART cohort, more frozen embryo transfer and fewer fresh IVF cycles have been performed with respect to the CTR cohort .The pART cohort included 749 subjects who underwent ART and met the inclusion criteria, 261  had positive serum β-hCG and 488 patients were failed to conceive. The CTR cohort included 844 subjects, 308  had positive serum β-hCG and 536 patients were failed to conceive. The statistical differences between the two groups were not found to be significant .In the pART and CTR cohorts, 40 out of 261  and 42 out of 308  subjects with positive serum β-hCG had a biochemical pregnancy, respectively. The comparison between the two groups is not significant, with a n = 49) and 0.212 ± 0.05 (CI = 95%); n = 56), in pART and CTR cohorts, respectively, with no statistically significant difference (p = 0.77). As for second trimester pregnancy loss, we documented four cases  in pART cohort among clinical pregnancies  and five cases  in the CTR cohort among clinical pregnancies , with a p- value of 0.95. We also documented one case of stillbirth both in pART cohort and one case in CTR cohort .Considering subjects with clinical pregnancy (ectopic pregnancies were excluded), the first trimester miscarriage rate was 0.223 ± 0.056 , we observed 165 (22.02%) deliveries of 176 babies compared to 202 (23.9%) deliveries of 226 babies in the CTR cohort (n = 844). The overall live birth rate remained, thus, unchanged during the pandemic with no statistically significant differences (p = 0.37). The live birth rate during the pandemic remains unchanged even when compared to our center's general rate between 2015 and 2019 .In the pART cohort  were tested positive for SARS-CoV-2 during the pregnancy in the pART cohort. The COVID-19 follow-up results are limited to patients with ongoing pregnancies.In our cohorts, we studied the impact of the COVID-19 pandemic on pregnancy outcomes among women who underwent ART treatments. A fertility center represents an ideal setting to study the impact of the COVID-19 pandemic on early pregnancy outcomes since all patients underwent predetermination and early follow-up despite the local restrictions.Many infertile patients decided not to request ART treatments due to the pandemic. During the pandemic, we witnessed a decline in the number of concluded ART cycles as compared to the precedent year (749 vs. 844 cycles). Moreover, the increase in the percentage of frozen embryo transfers with respect to fresh cycles suggests fewer new patients in the pART cohort . This dein vitro studies but remains, to date, theoretical  receptors to facilitate the fusion of viral and cellular target membranes. ACE2 protein is also expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle and may play a role in the decidualization process. ACE2 was also found in placental syncytiotrophoblast and cytotrophoblast samples from 7 weeks onward. The potential influence of the SARS-Cov-2 infection on early pregnancy outcomes was described in case reports and oretical –12.The available data, on the other hand, show that SARS-Cov-2 infection is not associated with an increased risk of early pregnancy loss and are in line with our results: an Italian case-control study showed no significant difference in the cumulative incidence of COVID-19 in women who experienced spontaneous abortion than in those with ongoing pregnancy . A DanisOther potential hazard factors for the outcome of ART pregnancies may be the pandemic state and the impact of social isolation. In the first few months of the pandemic, the community has self-isolated with significant inherent stress, fear, and economic instability , 15, 16.Nevertheless, our results demonstrate no statistical differences in the pregnancy loss rates between the COVID-19 and pre-COVID-19 periods. We also found no adverse effects in terms of implantation rate, early pregnancy loss, ectopic pregnancy, second-trimester pregnancy loss, or stillbirth. The overall success rate and the live birth rate remain unchanged with respect to the precedent years. It should be considered, therefore, efficacious to proceed with ART treatments during the pandemic.Other encouraging and interesting data are the very low incidence rates of COVID-19 infection among the pART cohort , less than the incidence (10.1%) in the general population or among pregnant patients , 25. OurIt is important to remember that pregnant women represent a population at high risk, and particular attention is paramount in such cases. Current data from the US Centers for Disease Control and Prevention (CDC) suggest that pregnant women might have an increased risk for severe COVID-19. Among women in reproductive age with COVID-19, pregnant women have an increased risk of hospitalization, intensive-care unit (ICU) admission, and receipt of mechanical ventilation, while mortality rates are similar . FurtherThe ART treatments should be performed, therefore, in security with restricted COVID-free protocols, prioritizing early vaccination. Recently, it has been suggested that the use of vitamin D and myo-inositol could represent a possible preventive treatment for pregnant patients with ART .In conclusion, we demonstrate that in patients with ART, the COVID-19 pandemic did not cause a statistically significant change in the live birth rate and in the pregnancy loss rate. Even though fewer ART cycles have been completed, the results are encouraging and support the decision to proceed with ART treatments throughout the pandemic.Our data support that ART during the pandemic is an effective and safe approach, similar to what was observed in a no pandemic period. Since infertility increases over time, and it is difficult to predict the end of the COVID-19 pandemic, infertile patients should ensure access to a viable opportunity to achieve a pregnancy. Patients and physicians should be reassured that pregnancy outcomes do not seem to be jeopardized by the pandemic state.The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author.This study was performed according to the principles of the Declaration of Helsinki (2013) and was approved by the Area Vasta Centro Ethics Committee . All data were fully anonymized before being analyzed in a secure database.MH, VN, and IR performed data analysis and wrote the manuscript. MEC conceived the idea, designed the study, and provided a critical review. FP helped with the data analysis. SB provided a critical review. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Since their discovery in the 1950s, rhinoviruses (RVs) have been recognized as a major causative agent of the “common cold” and cold-like illnesses, accounting for more than 50% of upper respiratory tract infections. However, more than that, respiratory viral infections are responsible for approximately 50% of asthma exacerbations in adults and 80% in children. In addition to causing exacerbations of asthma, COPD and other chronic lung diseases, RVs have also been implicated in the pathogenesis of lower respiratory tract infections including bronchiolitis and community acquired pneumonia. Finally, early life respiratory viral infections with RV have been associated with asthma development in children. Due to the vast genetic diversity of RVs (approximately 160 known serotypes), recurrent infection is common. RV infections are generally acquired in the community with transmission occurring via inhalation of aerosols, respiratory droplets or fomites. Following the outbreak of coronavirus disease 2019 (COVID-19), exposure to RV and other respiratory viruses was significantly reduced due to social-distancing, restrictions on social gatherings, and increased hygiene protocols. In the present review, we summarize the impact of COVID-19 preventative measures on the incidence of RV infection and its sequelae. Enterovirus within the Picornaviridae family, RV is a non-enveloped, positive-sense, single-stranded RNA virus with an icosahedric capsid containing a 7.2-kbp genome [RVs are the major etiologic agent for the “common cold”. First isolated in the 1950s , RV infep genome ,4. The vThere are three distinct RV species  comprising around 160 serotypes, each of which are categorized by nucleotide differences in the capsid protein regions and cellular receptor specificity. The majority of RV-A and RV-B serotypes (termed the “major group”) bind intercellular adhesion molecule 1 (ICAM-1) for host cell entry . ICAM-1 It was once thought that RVs did not contribute to lower respiratory tract disease. Based on part on the notion that RVs replicate more readily at 33 °C, the temperature of the nasal passage, compared to 37 °C, it was thought that RV could not infect the lower airways . HoweverRecent epidemiological studies using PCR-based assays have provided insight into the impact of RVs on more severe respiratory illnesses, in particular exacerbations of asthma, COPD and other chronic respiratory diseases. PCR-based studies looking at the prevalence of virus identification among various cohorts of patients with asthma when sick and well consistently show a higher prevalence of viral infection during exacerbations. Outpatient children who are sick with asthma exacerbations show anywhere from 62–81% positivity for viral infection versus only 12–41% of children who are well . PicornaAdditional information that viruses indeed cause attacks of chronic airways disease comes from an analysis of emergency department presentations for asthma and COPD over the course of a calendar year . ExacerbFinally, recent studies have implicated RV in viral bronchiolitis in infants, pneumonia and asthma development in children. RV is responsible for between 20–30% of all cases of bronchiolitis, and the most common cause in children 24 months or older . RVs werWhile there has been a great deal of progress in efforts to understand the immunological basis of RV infection, no effective antiviral treatments have been developed (reviewed in ). On theWhile PCR-based assays linking RV infection and asthma exacerbation are convincing, perhaps there has been no greater evidence of the link between respiratory viral infection and asthma exacerbation than the impact of COVID-19 on the incidence of asthma exacerbations in the United States and around the world. Following the initial surge of SARS-CoV-2 in March 2020, governmental agencies quickly developed a variety of preventative social restrictions in response to the mounting COVID-19 pandemic. At the height of the pandemic, remain-in-place orders and strict travel restrictions with enacted, nonessential personnel were encouraged to work remotely, large social gatherings and worship services were canceled, and educational institutions were closed. Since SARS-CoV-2 and RV are each transmitted via inhalation of respiratory droplets and aerosols, as well direct and indirect contact (fomites), the introduction and implementation of social distancing would be expected to “inadvertently” reduce the spread of RV and other respiratory viruses as well. Accordingly, the incidence of all non-COVID respiratory viruses decreased significantly during the height of strict COVID-19 pandemic measures, marked by social isolation and shelter-in-place orders.For example, at Bambino Gesù Children’s Hospital in Rome, the number of positive respiratory pathogen panels in patients admitted with respiratory symptoms decreased by 80% during the 2020–2021 winter season compared to the previous two seasons, 2018–2019 and 2019–2020 . The totA similar analysis was performed at the Children’s Hospital of Philadelphia, with a particular focus on health care utilization during the pre-lockdown (1 January 2015–17 March 2020), lockdown (18 March 2020 to 5 June 2020) and phased reopening (6 June 2020 to 15 November 2020) time periods . There wAt the University of California-Davis, the positivity rate for respiratory pathogen panels between 25 March 2020 and 31 July 2020 decreased to 9.88 positive results per 100 tests compared to 29.90 positive results per 100 tests in the previous five years . InfluenHowever, a closer look at the data reveals differences between the initial lockdown periods in the spring and summer of 2020, and the more relaxed protocols some countries employed in the fall of 2020. At that time, nurseries, kindergartens, primary schools, and many secondary schools had reopened. As noted above, school return has long been associated with RV infections . AccordiWhy was there a resurgence in RV compared to other respiratory viruses after the relaxation of social distancing measures? Due to its protein capsid, RV is more resistant to ethanol-containing disinfectant than viruses with a lipid envelope . ConsistThe disruption in normative transmission patterns of non-COVID respiratory viruses during the COVID-19 pandemic allowed a unique opportunity to analyze the effect of sociocultural factors on various viral-related illnesses, and the role of respiratory viruses in the pathogenesis of various diseases. A consortium of children’s hospitals in the United States compared the number of pediatric inpatient admissions for various diagnoses during the intensive COVID-19 lockdown period (15 March 2020 to 29 August 2020) compared to the same period in the previous three years . There wIn the aforementioned Philadelphia study , reductiAn observational study of 3100 subspecialist-treated adult patients with severe asthma in the U.S. showed significant reductions in exacerbations, emergency department visits and hospitalizations in April through August 2020 relative to the same months in 2019 . ExacerbA nationwide study of asthma hospitalizations in Japan showed a significant reduction in weeks 9 through 22 of 2020 compared to two earlier years . In KobeIn perhaps the largest relevant study, a retrospective analysis of 100,362 asthma patients from across England showed substantial and persistent reduction in asthma exacerbations over the 18 months after the first COVID-19 lockdown . Mean ex2) levels during the state of emergency [2 levels remained low when asthma exacerbations increased in the fall. The persistent reduction in asthma exacerbations after reopening of schools and businesses, in the face of increasing RV infections, is also poorly understood. Possibilities such as continued hygiene protocols and improved self-management have been proposed.While the most likely explanation for the substantial drop in asthma exacerbation rates seen during the pandemic is due to reduced exposure to respiratory viruses, other factors must also be considered. For example, the Hong Kong study  suggestsmergency . However1 and peak expiratory flow rate during the early months of the pandemic (March to June 2020), compared to questionnaire responses and pulmonary function measurements recorded during the year prior [As we have seen above, overall the impact of the social distancing measures has been a reduction in asthma exacerbations and improvement in asthma control. The Pediatric Asthma in Real Life (PeARL) multinational cohort study reported improved asthma control in 65.9% of pediatric patients ages 4–18 years along with significant improvements in pre-bronchodilator FEVar prior .However, in an individual patient, does the diagnosis of asthma increase the risk from COVID-19 infection? The preponderance of studies shows no increased risk of COVID-19 in asthma ,75,76,77In this review, we have prevented evidence that social-distancing, restrictions on social gatherings, and increased hygiene protocols designed to prevent COVID-19 reduced the prevalence of RV and other respiratory viral infections, leading to a reduction in asthma morbidity. However, recent evidence suggests that prior infections with RV or other respiratory viruses can attenuate the severity of SARS-CoV-2 infection. RV-A16 blocks SARS-CoV-2 replication in cultured airway epithelial cells  and RV-AFollowing the outbreak of COVID-19 in March 2020, social-distancing, restrictions on social gatherings, and increased hygiene protocols significantly reduced the opportunity for exposure to RV and other infectious agents. As a consequence, there was a significant reduction in both respiratory viral infections and asthma health care utilization. After school reopening in the fall of 2020, there was a specific increase in RV infections, in contrast to other respiratory viruses which remained diminished. School reopening was accompanied by a partial increase in asthma hospitalizations, but admissions remained lower than pre-COVID period. RV may be less susceptible to masking and disinfectants due to its small size and capsid coat. Just as family gatherings with young children drive asthma and COPD exacerbations in adults, younger children may be more likely to transmit SARS-CoV-2 infection to adults. Patients with allergic asthma do not suffer increased morbidity from SARS-CoV-2 infections, possibly due to the protective effects of IL-13 and other type 2 cytokines.


Tannins are polyphenols enriched in wood, bark, roots, leaves, seeds and fruits of a variety of plants. Over the last two decades, there has been an increasing interest in understanding the biological functions of tannins and their applications as antioxidants, anticancer drugs, and food additives. Since the outbreak of the COVID-19 pandemic, much effort has been devoted to finding an expedient cure. Tannins have been put forward as having possible anti-COVID-19 properties; however, owing to the profuse nature of the structurally diverse derivatives of tannins, the tannin species in the family associated with an indication of anti-COVID-19 have been poorly defined, compounded by frequent terminology misnomers. This article reviews the tannin family in fruits and the current knowledge about the activities of the compounds with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It will aid molecular and cellular biologists in developing natural anti-viral chemicals as means of overcoming the current and future pandemics. Beginning in early 2020, at time of writing the COVID-19 coronavirus pandemic has lasted for over two years, with about 507 million cases of infection and more than 6.2 million deaths . Several anti-COVID vaccines have been rushed into the clinic globally, debuting mRNA technology in vaccines. However, although vaccination has significantly reduced the extent and duration of symptoms, the efficacy of anti-viral immunity declines rapidly and breakthrough infections frequently occur even in the fully vaccinated population Considering the fact that living with infectious pathogens such as coronaviruses is likely to be a norm in the future world Characterization based on chemical structures classifies tannins into different categories: hydrolysable tannins, condensed tannins, complex tannins, and phlorotannins. Phlorotannins, are of low abundance and present mainly in brown macroalgae; however, tannins of the other categories are abundant in terrestrial plants Vitis vinifera Thaumatin-Like-1), resulting in conformational change of the protein VVTL1 as demonstrated by circular dichroism spectra in the near-UV region Table 1. Most grape-derived tannins are condensed tannins Some of the winemaking factors determining the flavor of wine products are the phenolic substances extracted from the seeds, skin, and stems of grapes as well as the wooden casks during the fermentation process. Due to technical limitations and short half-lives, the exact contents of tannic acid in different wines or fruits have been poorly characterized. Most studies measured the tannin content rather than tannic acid. It was indicated in some studies that hydrolysable tannins do not exist naturally in grape-derived wines Table 2). Tsuchiya et al., for example, showed that administration of a test beverage including 200 mg/day oligomeric procyanidins (condensed tannins) isolated from red wines improved skin condition of moisturizing and whitening in a group of 30-60 year-old healthy women in 12 weeks et al. reported that daily supplementation of resveratrol (19.2 mg) and polyphenols (136 mg) extracted from red wine for 8 weeks improved the metabolic profile including enhancing insulin sensitivity and decreasing serum low-density lipoprotein-cholesterol as well as triglyceride in non-diabetic individuals et al. demonstrated the anti-viral effects of persimmon-derived tannins against viruses including influenza virus, herpes simplex virus-1 and vesicular stomatitis virus by inhibition of viral infection The health benefit of red wine extracts as nutritional supplements is a popular topic on social media. However, little research provides controlled experimental evidence about the effects of red wine extracts on human subjects. The biological effects of tannins in natural products and wines have been investigated by different groups  The potential anti-tumor activities of tannins have been explored in numerous studies. The addition of tannic acid in cholangiocarcinoma chemotherapeutic regimens such as mitomycin C and 5-fluorouracil can achieve a synergistic effect which is believed to result from modulating the drug efflux pathways by tannic acid, thus increasing chemotherapy-induced apoptosis by the treatment It seems that the function of tannic acid in mediating oxidoreductive stresses is cell context dependent. In contrast to its anti-ROS anti-inflammatory cell-protective activities as observed in non-transformed cells, tannic acid induced apoptosis in prostate cancer cells through increasing the level of ROS, inducing ER stress, inhibiting tumor lipogenesis, and disrupting the plasma membrane as well as the nuclear structure + and CD8+ T lymphocytes have been observed in COVID-19 patients, especially in severe cases The two major frontiers in battling the COVID-19 are infection and propagation of the SARS-CoV-2 coronaviruses, and the possible extreme reaction of the body's immune system in response to pathogenic intrusion pro/3CLpro) to produce non-structural functional proteins essential for viral propagation  pro/3CLpro to inhibit the SARS-CoV-2 activity pro/3CLpro with IC50 ranging from 1 μM to 13.4 Μm 50 ranging from 2.31 μM to 50 μM 50 may result from the different methodologies such as fluorescence resonance energy transfer and ELISA-based enzymatic assays. Importantly, the dual inhibition of TMPRSS2 and Mpro/3CLpro by tannic acid can be translated into suppression of cellular entry of the virus pro/3CLpro by the tannins of dimeric proanthocyanidins in vitro studies.The transmembrane protease serine 2 TMPRSS2 is an essential cell surface protease which processes the viral surface spike protein (S protein) to enhance its binding to the cell surface receptor ACE2 (angiotensin converting enzyme 2) followed by cell entry via membrane fusion. The intracellular viral genomic RNA is then translated into polyproteins which are subject to further proteolytic cleavage by the viral main protease/3-chymotrypsin-like cysteine protease  filter coated with tannic acid has been developed which showed rapid and highly efficient capability to capture the influenza A virus, revealing a new application of tannic acid to constrain virus spread in vitro, compounds derived from modified tannins can be exploited for the development of anti-COVID drugs. Finally, it is worth exploring to determine whether combination of the tannin-based drugs with the FDA-approved COVID-19 medicines can enhance the therapeutic efficacy. The progression in these directions may also be applied to other viruses and help us prepare to fight the arising health-threatening pathogens in the future.As the world is evolving into the post-pandemic era of COVID-19 with potential unknown variants arising in the horizon, tapping the natural sources for safe and effective medication is an attractive resort. As summarized, a body of studies support that incorporating daily diet with the source food of anti-viral activity can have protective or ameliorating effects to curb viral infection. Thus, it is of high public interests to entail a clinically defined dieting practice for disease control. For example, the known concentrations of the different tannins required for viral inhibition can be used as a guidance to develop the formulae consisting of quality-defined natural products such as tea and fruits for daily consuming by the general population. Furthermore, given the potency of the tannin derivatives in curtailing SARS-CoV-2 infection


Squamous cell carcinoma (SCC) of the conjunctiva is a rare malignancy that is part of the spectrum of ocular surface squamous neoplasia (OSSN). Numerous non-modifiable and modifiable risk factors, such as male sex, age, cigarette smoking, and immunosuppression, have been identified. Any lesion of the conjunctiva requires a differential diagnosis between benign and malignant diseases, and all suspicious lesions should be biopsied.We present a case of SCC of the conjunctiva in a former smoker with multiple risk factors, including a previous SCC of the lower lip. Metastatic tumors rarely occur in the conjunctiva, but due to our patient's medical history, the exclusion of metastasis from the previous primary tumor was performed through whole-body imaging restaging. The patient underwent a no-touch wide resection, followed by adjuvant topical chemotherapy with 5-fluorouracil (5-FU). After finishing treatment, the patient continues to attend regular ophthalmology and oncology appointments.Increasing population awareness of modifiable risk factors for OSSN is essential. Misdiagnosis can lead to a loss of time in treatment and progression of the disease. Ocular surface squamous neoplasia (OSSN) represents lesions of the ocular surface that range from mild epithelial dysplasia to invasive squamous cell carcinoma (SCC) ,2. Most We present the case of a 64-year-old male patient with hypertension, dyslipidemia, type 2 diabetes mellitus, latent syphilis under surveillance, and a former smoker (96 pack years). The patient was under periodic follow-up in oncology consultations due to a local recurrence of an SCC of the lower lip, Tumor, Node, Metastasis (TNM) staging pT2N1M0 of the American Joint Committee on Cancer (AJCC) 8th edition, in January 2021, having undergone surgery followed by adjuvant chemoradiotherapy  until May 2021. On August 2021, the patient started to complain of eye irritation and progressive growth on the surface of the right eye (RE)  with poorly defined limits, appearing to extend to the upper eyelid and infiltrating the lacrimal gland Figure .On CT of the face and neck and whole-body positron emission tomography/CT with the glucose analog 2-[18F] fluoro-2-deoxy-d-glucose (FDG-PET/CT), there was no evidence of local or distant recurrence of the SCC of the lower lip.The patient was referred to the ophthalmology department of a tertiary medical center and underwent a no-touch wide resection of the conjunctival lesion in February 2022. The lesion was located in the inferior temporal quadrant of the bulbar conjunctiva without the involvement of superior or inferior tarsal conjunctiva. Infiltration to the underlying scleral tissue was denoted during the procedure. Cryotherapy was applied to the wound bed and the resection bed's edges. Sponges soaked in MMC 0.02% were then applied to the wound bed and conjunctival edges for three minutes, after which a cryo-preserved human amniotic membrane was sutured, epithelial base-up, to cover the conjunctival defect. The histopathologic examination of the surgical sample confirmed a well-differentiated SCC, with invasion through the conjunctival basement membrane, TNM staging pT2cN0cM0 (AJCC 8th Edition). At the Head and Neck Cancer multidisciplinary team meeting, a decision was made to initiate adjuvant treatment with topical chemotherapy. A 5-FU 1% topical solution was applied four times daily in the RE starting in March 2022. After completing two one-week cycles of topical treatment, the patient presented mild ocular surface toxicity with superficial punctate keratitis and two small corneal erosions, which were successfully treated with topical ofloxacin and carbomer, along with the suspension of topical 5-FU for one week. In total, three one-week cycles of topical 5-FU were completed. The decision to finish treatment with 5-FU was made upon the absence of clinical evidence of recurrence. Ophthalmologic consultations were attended weekly during adjuvant topical chemotherapy. On subsequent ophthalmologic consultations until November 2022, there was no evidence of recurrence in the RE Figure . The patInvasive SCC of the conjunctiva is a rare malignancy that is part of the spectrum of ocular OSSN . NumerouThe gold standard for diagnosis is histopathologic evaluation following an incisional or excisional biopsy of the conjunctival lesion . The casMetastatic tumors rarely occur in the conjunctiva, but conjunctival metastasis has been described in relation to breast carcinoma, cutaneous melanoma, and other primary tumors . Since oThe management of OSSN includes either surgical or medical treatment or a combination of both modalities. The treatment choice depends upon factors such as the patient's age and systemic comorbidities, prior treatments, and ability to comply with medications or to undergo surgery. In patients with documented orbital or intraocular invasion, orbital exenteration or enucleation/radiotherapy may be needed, respectively, and consultation with oculoplastics specialists is required. Standard surgical management includes the traditional no-touch wide resection technique , a proceHistopathologic examination revealed invasion through the conjunctival basement membrane in a well-differentiated SCC, TNM staging pT2cN0cM0 (AJCC 8th Edition). Therefore, a decision was made to proceed to adjuvant topical chemotherapy. Topical chemotherapeutic and immunomodulatory agents, such as 5-FU, MMC, and INF-α2b, are drugs that have been used both as monotherapy and post-operatively in managing OSSN . Its useSCC of the conjunctiva is a rare but curable malignancy, and in the presence of a suspicious conjunctival lesion, a very low threshold for biopsy should be maintained to make the diagnosis of SCC at its earliest. Misdiagnosis can lead to a loss of time in treatment and, in the worst case, the progression of the disease to a life-threatening state. Recurrence after the primary excision is frequent, and it is essential to maintain a strict follow-up plan.


Elevated PHQ scores were found after the onset of the COVID-19 pandemic. After the initial peak in fall 2020, scores decreased but did not reach pre-pandemic levels.Adolescent behavioral health was in crisis before COVID-19. The shutdown and reopening of in-person learning and extracurricular activities may have worsened this crisis. We examined high school athletes’ depression before and during the pandemic. Data were collected as part of a pilot program incorporating Patient Health Questionnaire (PHQ) screenings during high school sports physicals before the COVID-19 lockdown and three timepoints after. Statistical comparisons were made using logistic regression. A total of 927 individual scores were analyzed: 385 from spring 2020; 145 from fall 2020; 163 from fall 2021; and 234 from spring 2022. Fall 2020 students were 3.7 times more likely to have elevated PHQ-2 scores than spring 2020 students . Fall 2021 and spring 2022 scores did not differ significantly from pre-pandemic, although trends of elevated scores persisted . A significant difference in PHQ-9 depression severity classification was detected over time ( Countermeasures to the spread of COVID-19 led to major changes in daily living to mitigate the global loss of life ,5,6,7,8.One subgroup of adolescents that warrant further investigation is high school sport participants. School closures resulted in the cancellation of all, or most, extracurricular activities and these students may have lost more than simply the social interaction from school classmates. Given that physical exercise has shown to be protective against depressive symptoms in adolescents , the losData from a pilot program that incorporated depression screening in high school athletic physical exams at a large suburban high school was used. Utilizing this previously collected data allowed us to compare athlete depression screening results before and after the COVID-19 pandemic lockdown was implemented. These screenings are part of the school sponsored physicals that student athletes voluntarily attended to obtain medical clearance for high school sports participation.The Patient Health Questionnaire-2 (PHQ-2) and Patient Health Questionnaire-9 (PHQ-9) are screening tools for depression that can be self-administered and are validated for use in adolescents ,28,29,30The PHQ-9 is also self-administered, consisting of nine screening items developed to assist in making a diagnosis of a depressive disorder . Scores This study utilized deidentified previously collected data. The analysis of these deidentified data was approved by our institutional review board. The school health program through which the data were collected obtained consent for school sports physicals, which included the depression screening. The students in this data include adolescents between the ages of 13 and 17 who intend to obtain medical clearance for participation in high school sports. As part of the school physical, students were given the PHQ-2 on paper to fill out. After completing the PHQ-2, a monitor collected and immediately scored the screeners. Students scoring less than 3 were excused and students scoring 3 or higher were identified as positive on the PHQ-2 and given the PHQ-9. PHQ-9 scores were scored immediately, and students were directed to their next station based on score: scores of 0 on question 9 (assessing suicide risk) in conjunction with a total score between 0 and 9 were given information about mental health and depression. Scores of 1 or higher on question 9 or a total score higher than 10 were seen by a licensed clinical social worker for further assessment of suicide and depression risk, as well as developing an appropriate treatment or referral plan.The initial screenings in spring 2020 occurred one month before the state’s COVID-19 countermeasures went into effect. The second screening in fall 2020 occurred when a delayed start to organized high school athletics was planned in the academic calendar. There were also significant COVID-19 safety protocols implemented based on level of contact within each sport. The third and fourth screening, fall 2021 and spring 2022, respectively, occurred when high school sports had resumed playing its normal seasonal schedule.Deidentified PHQ-2 and PHQ-9 scores along with limited student demographics were entered into a database and made available for analysis. To improve accuracy of self-reported demographic information, the demographics portion of the survey was simplified from free response questions to categorical check-box responses with the option to write in if categorical options were not appropriate. This led to a shift in demographics between fall 2020 and fall 2021. To address repeated measure concerns, randomly selected scores for students who attended multiple sessions were used for analysis. Data were analyzed using STATA 16  . InitialAfter accounting for repeated measures, data from 927 students were analyzed. For the PHQ-2 scores, there were 385 in spring 2020, 145 in fall 2020, 163 in fall 2021, and 234 in spring 2022. Demographic characteristics of students sampled at each period are presented in p = 0.03). The proportion of students scoring 3 or higher on the PHQ-2 was 6% in the pre-pandemic group, then rose to 14% in fall 2020, and has been at 9% for fall 2021 and spring 2022. Students who attended in fall 2020 had a 3.7 times increased odds of scoring 3 or higher on the PHQ-2  compared to students in spring 2020 (pre-pandemic)  .p < 0.01). The change in distribution of PHQ-9 scores after the onset of the pandemic identified a greater proportion of scores persisting at the moderate and the moderately severe depression severity classification.There were PHQ-9 results available for analysis from 25 students assessed in spring 2020, 18 in fall 2020, 14 in fall 2021, and 23 in spring 2022 . The medThe arrival of COVID-19 in the United States produced far-reaching uncertainty as well as profoundly impacting communities nationwide. With sports programs playing a large role in many student athletes’ lives, the suspension of these programs created additional hardships for at least some of these adolescents during an already stressful period. Our findings identified a significant increased odds of depression demonstrated by elevated PHQ scores among high school athletes associated with timing of the COVID-19 pandemic lockdown. Although not statistically significant, the elevated odds ratios for the fall 2021 and spring 2022 PHQ-2 scores indicate that this trend may be persisting over time. While these changes coincide with the timing of the COVID-19 lockdown, other factors beyond school athletics could have influenced the changes in screening scores.We also found that female gender and Hispanic ethnicity were independently associated with increased depression risk. Sub-analysis of data comparing only the initial lock-down period  to pre-pandemic spring 2020 did not find gender or ethnicity to be independently associated with elevated PHQ-2 scores. Only the timing of assessment was found to be associated with elevated scores. This may reflect the overwhelming effect timing of the initial lock-down had on all student athletes. This adverse effect could also have been further fueled by the lack of understanding and general anxiety surrounding COVID-19 during the initial lockdown. It is encouraging that although the rates of depression remained elevated relative to the base-line pre-pandemic rate, the rate did decrease from the initial post-pandemic measure and may be indicative of resiliency among high-school athletes associated with or independent of their return to sports. Future studies of high school athletes, and adolescents in general, are warranted to understand how they have and continue to respond to the everchanging pandemic.For the overall PHQ-9 scores, a consistently increasing median over time is concerning but our limited sample size prevented further analysis. The PHQ-9 score median changed depression severity classification from mild to moderate depression. Although a statistically significant shift in PHQ-9 score distribution was noted, no student scored 20 or higher (severe depression classification) in the three post-pandemic screenings.Consistent with trends noted in the recent literature, the timeline of the lockdown has been associated with declining mental health of this subgroup of adolescents ,24,25,26Our findings are limited to a single high school and, therefore, may not be generalizable to other schools. Some students may have received their school athletic physical from their own physician, so these results may not be representative of all student athletes at this or other schools. The voluntary nature of the screening event, as well as other potential outside factors such as fear regarding large crowds, may have discouraged students from attending the event post initial COVID-19 lockdown. Our results may not be generalizable to other age groups and further research should be carried out to assess what, if any, persistent effect the lockdown might have had on other school-aged students. If conditions allow, it would be ideal to have repeated measures over time from each participant to access changes in screening scores in further research. Assessing different outcomes based on differing levels of lockdown or self-isolation would also be a potential area for exploration. Self-reported data are subject to bias. Students completing a mental health screener may have underscored their responses to avoid being identified or to avoid further screenings. If students were afraid to be identified for depression, it is possible that our results underestimate the true effect the pandemic may have on adolescent depression.Other studies that used data collected via social media or at a single point in time, make it difficult to evaluate changes in depression scores over time in similar samples of individuals. We are providing a unique insight into the magnitude of change in depression screening scores potentially due to the pandemic shutdown. Previous studies also completed their data collection a few months after the initial lockdown. Our data are also unique given the baseline screenings collected in the weeks leading up to lockdown protocols going into effect. Uncertainty around the pandemic was most likely more prevalent and coping strategies less so during those early months after lockdown restrictions were implemented.There are several potential reasons why the mental health of high school athletes deteriorated, including reduction in physical activity, lack of community and familial support, or vulnerable socioeconomic positions ,20,21,22Expansion to other high school students may be warranted to understand how the pandemic or other events are affecting high school students’ mental health. These results support the necessity of vigilant attention on the mental health and wellbeing of high school students, particularly given the interruption of high school athletics post COVID-19 lockdown.The timing of these initial screenings provided a unique opportunity to examine depression risk immediately before and after pandemic countermeasures went into effect. Further understanding of adolescent athlete depression can facilitate the needed response to address this growing need. When high school athletes were separated from the benefits provided by organized school sports, such as physical activity level and social interactions, we saw an increase in the number of athletes scoring higher on depression screeners. Implementing mental health screening into routine physicals helped identify those potentially in need of early depression treatment in response to outside influences on mental health status.


Vertebral arthrodesis for degenerative pathology of the lumbar spine still remains burdened by clinical problems with significant negative results. The introduction of the sagittal balance assessment with the evaluation of the meaning of pelvic parameters and spinopelvic (PI-LL) mismatch offered new evaluation criteria for this widespread pathology, but there is a lack of consistent evidence on long-term outcome.The authors performed an extensive systematic review of literature, with the aim to identify all potentially relevant studies about the role and usefulness of the restoration or the assessment of Sagittal balance in lumbar degenerative disease. They present the study protocol RELApSE (NCT05448092 ID) and discuss the rationale through a comprehensive literature review.From the 237 papers on this topic, a total of 176 articles were selected in this review. The analysis of these literature data shows sparse and variable evidence. There are no observations or guidelines about the value of lordosis restoration or PI-LL mismatch. Most of the works in the literature are retrospective, monocentric, based on small populations, and often address the topic evaluation partially.The RELApSE study is based on the possibility of comparing a heterogeneous population by pathology and different surgical technical options on some homogeneous clinical and anatomic-radiological measures aiming to understanding the value that global lumbar and segmental lordosis, distribution of lordosis, pelvic tilt, and PI-LL mismatch may have on clinical outcome in lumbar degenerative pathology and on the occurrence of adjacent segment disease. We conducted a comprehensive review of literature about this topic and here we propose our upcoming prospective study. The RELApSE study is, to our knowledge, the first prospective and multicenter study on these topics. We present the study protocol registered on 22.1Interbody fusion, including: transforaminal (TLIF), posterior (PLIF), anterior (ALIF), and lateral (LLIF); effectively treat lumbar degenerative pathology and provide spinopelvic balance and the impact of the interbody approach on segmental and adjacent level lordosis could be an important factor to consider during pre-operative planning to achieve pre-specified alignment goals.,,,,From the literature search conducted , 176 pap3The English literature is systematically investigate using MEDLINE, the NIH Library, Pubmed, web of science and Google Scholar according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, with the aim to identify all potentially relevant studies about the role and usefulness of the restoration or the assessment of Sagittal balance in lumbar degenerative disease. Searching for relevant studies, the reference section of included articles was analyzed.The search was performed typing the following items (Pelvic incidence) AND (mismatch) (Pelvic incidence-lumbar lordosis) AND (mismatch) (PI-LL) AND (mismatch) (PI-LL) AND  (Pelvic incidence-lumbar lordosis) AND , obtaining 237 potentially titles.-Availability of full-text articles-English text only-Patients older than 18-year-old without history of trauma-Use of Sagittal balance parameters to select, plan or evaluate the treatment;-Presence of neurological outcome evaluation. No specific limitation was applied regarding the timing of neurological evaluation after treatment.-Papers published from 1985 onwards (for availability of recent imaging studies such MRI) Conversely, exclusion criteria were:-Full-text articles in languages other than English-Studies reporting patients with post-traumatic disease, other spinal segment considered-Patients younger than18-year-old-No data available about neurological outcome or not focused on clinical outcomeThe first step of selection was focusing the usefulness of the study of Sagittal balance parameters in lumbar degenerative disease. In this regard, we chose to exclude by title and abstract papers that dealt with other segments of the spine, non-degenerative conditions such as congenital and pediatric forms, and discarding publications that had other languages outside of English, obtaining through these initial inclusion criteria 201 potentially relevant articles. As further criterion of inclusion, we chose to consider adult populations with just degenerative conditions (excluding post-traumatic disease). It is worthwhile note that neurosurgical intervention was not considered as a criterion of inclusion itself since both patients eligible for neurosurgical treatment and non-surgical patients has been included. Given these premises, we selected papers according to the following inclusion criteria.Data extracted from each study were (1) authors, (2) year of publication, (3) study design, (4) purpose of the study, (5) disease condition, (6) number of patients included, (7) PI-LL parameters used, (8) lumbar spine segment evaluated, (9), neurological functions evaluated (10) clinical outcome (11).3.1A total of 237 studies were found through PubMed database search and reference section screening. Duplicates check was carried out by an automatic tool working on Microsoft Excel spreadsheets. Out of the initial papers, 1 duplicate, 20 were out of topic identifiable by the title, 9 with other languages, were removed; thus 201 titles with abstract were identified and, following the eligibility criteria, 185 papers were screened. A further qualitative skimming led to articles being selected for full text screening, out of which a total of 176 articles were included in the systematic review .3.2The study aims to evaluate the relationships between radiological data and patients' reported outcome. Starting from a heterogeneous population in terms of clinical conditions, pathology, and surgical treatment options, the study method is to make the population homogeneous on some data available in all patient's end that can be analyzed independently. These data are pelvic parameters , segmental lumbar lordosis (LS), global lumbar lordosis (LL), PI-LL mismatch, and L4-S1/LL lordosis ratio; clinical results based on administered questionnaires  and overall outcome assessment at FU , good , fair (improvement compared to preoperative but still with relevant symptoms), unchanged (symptoms similar to preoperative), negative (worsening of symptoms compared to preoperative); severely worsened ; occurrence of symptomatic junctional pathology (yes/no), need for surgical revision of the operated level (yes/no) or of the adjacent level (yes/no).3.3Primary end-point: analysis of the relationship between clinical results  and pelvic parameters, overall lumbar/segmental postoperative lordosis/ratio L4-S1-overall lumbar lordosis  in the hypothesis that the persistence of elevated PI-LL mismatch, reduced LL or altered pelvic parameters (pelvic tilt) may represent independent adverse prognostic factors for patients reported outcome, the occurrence of symptomatic junctional pathology and need for surgical revision.Secondary end-points: 1) Comparison between different interbody fusion techniques (Anterior Lumbar Interbody Fusion (ALIF) vs. Posterior Lumbar Interbody Fusion (PLIF) vs. Transforaminal Lumbar Interbody Fusion (TLIF) vs. Extreme lateral Lumbar Interbody Fusion (XLIF)) in terms of increasing segmental lordosis; 2) Comparison between different interbody fusion techniques (ALIF vs. PLIF vs TLIF vs. XLIF) in terms of changing the global lumbar lordosis, spinopelvic parameters and PI-LL mismatch; 3) Long-term evaluation of lumbar lordosis stability in relation with occurrence of subsidence or pedicular screws failure.3.4The sample size is assessed in relation to the primary objective. We want to compare the variation in clinical parameters before and after the intervention  between the groups finally identified by the presence/absence of LL-PI mismatch.In the hypothesis of no difference, the data necessary for the calculation will be referred to as reported by Divi et alt-test with a minimum sample size of 362 subjects is required. Since the study is multicentric and considering the risk of loss of information during follow-up or the presence of incorrect preoperative radiographic examinations, the enrollment of a total of 500 patients is considered exhaustive. The evaluation of the secondary end-points, which is not essential, will be carried out on the same population sample.The significance is appointed at 0.05, a test power of 0.95, assuming to compare the two samples using a two-tailed t-test and ANOVA . The correlation between numerical variables will be evaluated through Pearson's correlation coefficient and relative test . Any linear or non-linear regressions will be assessed for the relationship between lumbar lordosis delta, pelvic parameters, and clinical improvement. Depending on the results provided by the analyzes described, it may be appropriate to set up mixed-effects models to assess the longitudinal trend of the study parameters. The possible implementation of non-parametric models of supervised machine learning  will be evaluated to verify the actual predictive power of the variables under consideration concerning the clinical evaluation.Quantitative variables will be expressed using means and standard deviations (medians and quartiles when appropriate). A comparison of proportions will be performed with the Chi-squared test for categorical variables. Qualitative data will be expressed as a raw number and a population percentage. Continuous variables will be compared using the Student Due to the nature of the multicentre study and the high sample size, it is planned to create an interactive report (dashboard) for viewing the statistical results obtained.3.5The participant's investigators will be identify in the Italian context among orthopedics or neurosurgeons with proven experience in the field of vertebral surgery  by direct invitation from one of the steering committee members. Surgeons interested in the study must sign a letter of intent to underline the commitment required and the roles of the investigator. Each participating investigator is required to obtain approval from their relevant ethics committee. Investigators will recruit patients in the context of their regular clinical and surgical activity. Recruitment must be prospective, and the patient must be enroll before surgery to avoid selection bias related to clinical results. Each participating surgeon will be required to recruit a minimum of 20 complete and evaluable patients to be included in the investigators, while the number of patients enrolled should not exceed 60 cases for the single surgeon with the objective to homogenize the contribution of individual investigators and avoiding, within the enrolled population, excessive imbalances and discrepancies. Once the programmed sample size has been reached, recruitment will be close. Eventually for some centers and some surgeons, consideration will be given to stratifying patients as private, insured or government-funded and whether they have claims or demands.3.61.Patients undergoing to an instrumented lumbar arthrodesis operation at 1, 2, or 3 levels2.Age between 18 and 75 years3.Agree to inclusion in the study with a subscription of informed consent, available for five years follow-up, including phone interviews.4.Availability of adequate preoperative radiological documentation: CT or MRI of the lumbar spine; standing lumbar spine x-ray performed in a neutral position in which the pelvic parameters  and all lumbar segments can be correctly assessed5.Availability of adequate and comprehensive clinical information, including the presence of preoperative ODI and SF-126.Availability of adequate information regarding surgery7.Availability of postoperative radiological documentation: lumbar spine X-ray with the exact requirements as point 4 performed in the postoperative period and at one year follow-up.8.Availability of adequate and comprehensive clinical information, including ODI score and SF-12 questionnaire at follow-up. The minimum follow-up for each patient included must be 12 months, to be continued for a total of 5 years.All patients with the following requirements will be included in the observational study.Patients who, although already enrolled, do not meet the inclusion criteria at final evaluation will be excluded. Patients with a life expectancy of fewer than 5 years due to associated diseases must be excluded from the study.Patients who, for various reasons, have to withdraw their consent to be included in the study will also be excluded. There are no other exclusion criteria.3.7-general: age, sex, smoking habit, previous diagnosis of osteoporosis-surgical data: type of surgery performed, kind of arthrodesis performed, date of surgery, used cages material, used cage lordosis degrees, intraoperative adverse events, ODI, technical errors, complications, hardware failure, need for reoperation, the occurrence of junctional pathology, intervention-junctional pathology time-clinical data: diagnosis (type of degenerative disease), duration of symptoms, presence of claudication or radicular pain, presence of neurological deficits, presence of L5 sacralization, ODI score, SF-12 PCS, SF-12 MCS, days of postoperative hospitalization, overall outcome assessment. ODI score and the SF-12 questionnaire  are used for outcome evaluation.-radiological data: overall lumbar lordosis, segmental lordosis of all lumbar levels, pelvic incidence, pelvic tilt, sacral slope. The values will be calculated according to the criteria reported by Duval-Beaupère. From these data, theoretical pelvic tilt will be subsequently calculated regarding Vialle's formula (PT = PI x 0.37–7), pelvic delta tilt , PI-LL mismatch , L4-S1 lordosis/LL lordosis (percentage). The vertical sagittal axis (SVA C7–S1) is not considered in this study about the need to obtain teleradiography of the entire spine, a non-routine and mainly not required examination for degenerative diseases.For the recruited patients, all the following data are collected.www.surgimap.com where all the policies and conditions of use are visible.All images must be centralized for measurements anonymously and coded. All radiological data, measured as angles or derived numbers, will be calculated by independent data managers recruited as volunteers among medical specialists or fellows (see Study Board). The angle values will be calculated by performing three successive measurements on the same radiological image by three independent examiners not involved in the surgical management. Subsequent calculation of the average of the nine values is obtained. Calculating pelvic angles and parameters can be done with freeware SurgimapÒ software developed by a group of vertebral surgeons and engineers to support anatomical evaluation and surgical planning . The software can be downloaded free from the website 3.8All patient follow up continues, unless the patient withdraws consent explicitly, for the entire study duration initially planned for five years.The follow-up includes postoperative clinical evaluation three months after surgery, one year and up to 5 years annually. Any additional assessment will be dictated only by clinical needs and must be added to the follow-up with a related time of occurrence. The follow-up evaluations must include acquiring all clinical data, including ODI and SF-12 evaluation questionnaires. Follow-up is IN the responsibility of a single investigator. A telephone assessment may be performed on patients who are not available for outpatient assessments or who cannot be reached by completing ODI and SF-12 by interview.,,The follow-up must also include the acquisition of a lumbar spine standing X-ray at three months and 12 months, as normally suggested by good clinical practice. According to the literature, implant settlement and cages subsidence occur mainly in the first 12 months.3.9trials.gov with NCT05448092 ID (protocol ID 012022). No interference is foreseen on the patient's diagnostic-therapeutic path or technical treatment options chosen by participating surgeons. Furthermore, no form of experimentation with techniques or materials is envisaged. Data collection is prospective in the context of regular clinical activity. The study is not sponsored. The management of privacy and personal data is in full compliance with the current Italian law. The study guarantees the transmission and collection of data in a completely anonymous form. The study is observational and not sponsored and only represents an analysis and comparison of data obteined from regular clinical and surgical activity. No experimentation is envisage. There are no conflicts of interest for any of the board members.RELApSE is a purely observational study registered and published on 3.10The supervision of the study provides for the verification of the patient's record completeness, the adequacy of the radiographs for the purpose of the study, and the correct presence of follow-ups. Random evaluation of the accuracy of the measurements. Evaluation of proper data analysis procedures. Participation and supervision of the results analysis. Supervision is carried out by independent figures who are not part of the study board and are not investigators of the study.A telephone evaluation will be performed anonymously on a sample of enrolled patients representative of all investigators to verify the data's accuracy and truthfulness.4The latest AANS guidelines on arthrodesis for degenerative pathology part 7–12, 2014)–12, 2014A recent systematic meta-analysis highlighted a strong relationship between LBP and reduced lumbar lordotic curve mainly when patients were analyzed with age-matched healthy controls.,,p = 0.043) as well as more back pain.Furthermore, postoperative reduction of pelvic tilt was associated with better outcomes after PLIF surgery for spondylolisthesisBetter improvement of PI-LL mismatch with reduced PT and higher LL was found in patients without residual back pain after the OLIF procedure,On the contrary, Hsu et al reported no correlation between LL or LL restoration ratio and the outcome of patients undergoing PLIF for degenerative spondylolisthesis,P > 0.05). This study suggests that limited surgery addressed to focal neurological disease has equivalent effects of corrective surgery.A recent large retrospective study shows that patient outcomes in short-segment lumbar fusion for the degenerative lumbar disease are equivalent in patients with and without a postoperative PI-LL mismatch at one year follow-up. The two groups' preoperative, postoperative, or delta outcome scores  were noted. PI-LL mismatch was not found to be an independent predictor for patient-reported outcome on multivariate analysis (Adjacent segment degeneration (ASD) after lumbar arthrodesis, both symptomatic and radiological, is a well-known problem. Many studies discuss this topic, and several aspects were analyzed as causes or risk factors. A prospective study by Ekman shows that surgical fusion accelerates the occurrence of degenerative discopathy at the adjacent level compared with natural history.65,,,,,,,In 2001 Kumar et al firstly reported a significant association between ASD and the C7 sagittal plumb line. A vertical sacrum was highly associated with ASD even with regular C7 plumb line. Sacral inclination was considered an essential aspect of sagittal alignment as an expression of the compensation mechanism.The relationship between pelvic parameters and ASD was also studied. Nakashima et al identified a high degree of pelvic incidence as a risk factor for early-onset radiological ASD, probably in relation to the reduced probability of obtaining appropriate lordosis after surgery.,,,Some authors found a significant reduction of sacral slope angle in patients with ASD.On the contrary, some authors have highlighted the absence of a relationship between ASD and sagittal alignment. Anandjiwala et al reported that LL is not a risk factor for ASD occurrence,The analysis of these literature data shows sparse and variable evidence. It highlights how clarification and greater understanding of this argument are still needed, evoking the need for methodologically correct and high-level studies.This study is not sponsored, and there are no conflicts of interest within the steering committee or for single investigators in front of the final results. The study is dedicated to the memory of Vincenzo Di Stefano, an excellent friend, person, and vertebral neurosurgeon.


The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has affected day-to-day life worldwide and presents an unprecedented challenge to public health. Many countries performed mitigation measures to contain the disease spread and break the exponential curve. Omicron had already become a dominant variant in Myanmar and then, the fourth wave of the COVID-19 epidemic started on 28th January 2022. Myanmar performed the main community mitigation measures such as strict quarantine for the people who came back from foreign countries, expansion of testing capacity, enforcement of non-pharmaceutical interventions, and improvement of COVID-19 vaccination coverage. Although decreasing the number of COVID-19 cases and deaths, Myanmar is facing the challenges such as human resource shortages in the health sector, community trust for vaccine safety, and inequitable vaccine demand. This communication intends to give insights on what should be considered as the proper mitigation measures to contain the disease spread through the community and as the challenges that occur in implementing public health and social measures. In the current world, many countries are experiencing different waves of coronavirus disease 2019 (COVID-19) due to the respective dominant variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . IncidenMyanmar launched the COVID-19 vaccination program in January 2021 according to the National Deployment Plan (NDP) . COVID-1www.mohs.gov.mm) and social media page . People who enter from foreign countries through the international airports and ground crossings have to follow the strict quarantine and COVID-19 testing procedures. MOH is also implementing the mitigation measures such as the expansion of testing capacity in both public and private sectors, development of the teleconsultation teams with 24-hour service for people isolated at home, the establishment of rapid response teams linking with COVID-19 test centers and hospital bed management committee, and providing of the treatment at designated treatment centers, and vaccination to the people with targeted groups.MOH has been reporting to the public about the daily confirmed cases [tested by reverse transcription polymerase chain reaction (RT-PCR) and rapid diagnostic test] and deaths, risk communication messages, updated information including COVID-19 vaccination, updated standard operating procedures and guidelines regarding prevention and control measures, and health education facts on the official web page (As a SARS-CoV-2 strain surveillance, the genomic sequencing was being performed on the RT-PCR positive samples of some local persons and the people who returned from foreign countries by international flights and cross-border points of entry. Samples from the patients who acquired the infection outside of Myanmar were sequenced but no secondary infections. MOH occasionally announced the news of detected COVID-19 variants. On 18th March 2022, BA.2 sublineage of Omicron variant was detected in 31 specimens tested and a total of 433 confirmed cases with Omicron variant were detected up to 30th April 2022. According to the NDP, in January 2022, booster dose vaccination started in high-risk groups such as frontline healthcare workers and people aged 40 years and above. Up to 30th April 2022, 52.7 million of COVID-19 vaccine doses have been administered and there were 22.5 million people who were fully vaccinated, and 6.5 million people administered first doses of COVID-19 vaccine [In case the coronavirus spreads through the population, the new variants will continue to happen, and then other families of the Omicron variant can continue to emerge. Therefore, the continuation of non-pharmaceutical interventions, real-time disease surveillance, rapid case identification and response, implementing health education and health literacy promotion, improving vaccination coverage, and providing booster doses for all prioritized people should perform to reduce the disease spread. Community participation is crucial to the effective prevention and control of COVID-19. This communication can give the benefit that the countries can adapt to the best practices of the COVID-19 mitigation measures from Myanmar to reduce the disease transmission and prepare for the new wave of the pandemic.


Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a defect in the branched-chain alpha-ketoacid dehydrogenase complex (BCKDC). This leads to the accumulation of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, which can cause neurotoxicity. Patients with MSUD are carefully managed from birth with dietary restrictions and can acutely decompensate in the setting of infections or injury.We present the case of a 29-year-old female with a history of MSUD and rheumatoid arthritis on methotrexate and adalimumab who presented to our emergency department with symptoms suggestive of a metabolic crisis including nausea, vomiting, and presyncope. She was diagnosed with coronavirus disease 2019 (COVID-19) and admitted. An initial leucine level was mildly elevated at 253 μmol/L, consistent with her underlying metabolic condition. She was placed on an infusion of normal saline and 10% Dextrose (D10) in addition to a protein-restricted sick-day diet. Remdesivir therapy was initiated due to her immunocompromised status and high risk for decompensation but had to be discontinued due to nausea and vomiting that negatively impacted the patient’s oral intake. Her leucine level peaked at 647 μmol/L; however, her neurologic examination remained benign without signs of cerebral edema. With prompt involvement of our metabolic genetics team and initiation of intravenous fluids and the sick-day diet protocol, we avoided a metabolic crisis. The patient was discharged on day 5 of hospitalization with no complications from COVID-19 infection.This case highlights the individualized approach to the treatment of COVID-19 infection in a patient with a metabolic disorder. COVID-19 infection in the setting of MSUD has only been reported in two prior publications, one being a severe metabolic crisis with neurologic involvement. Fortunately, our patient experienced a mild case of COVID-19 without significant respiratory symptoms, and we were able to prevent a metabolic crisis during admission. Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of metabolism characterized by a defect in the branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) that affects about one in every 185,000 live births worldwide . This enA 29-year-old female with MSUD and rheumatoid arthritis on methotrexate and adalimumab presented to the emergency department with one day of acute onset headache, dizziness, nausea, and non-bloody, non-bilious vomiting. This presentation was consistent with MSUD-related metabolic crises she has had in the past. She had been restricting her dietary protein intake at home prior to presentation. She contacted the on-call geneticist when her symptoms failed to resolve and was instructed to present to the emergency department. Vital signs on presentation were as follows: temperature, 99.1°F; heart rate, 106 beats per minute; respiratory rate, 21 breaths per minute; blood pressure, 126/86; and oxygen saturation, 97% on room air. A physical examination was only notable for dysarthria and decreased strength and tone in the bilateral lower extremities, consistent with her neurologic baseline. The remainder of the neurologic examination was benign and nonsuggestive of cerebral edema, one of the serious complications of an MSUD metabolic crisis. Basic laboratory values were only notable for elevated alkaline phosphatase of 139 u/L (reference range: 37-117 u/L). A complete blood count was normal with a differential notable for lymphocytopenia. An amino acid panel was obtained  along with the sick-day diet protocol, which is a dietary intervention that aims to prevent skeletal muscle catabolism and promote protein anabolism. The sick-day diet prescription typically involves increasing daily caloric intake to 120%-150% of daily energy expenditure with a restriction of leucine intake by 50%-100% , so the The patient experienced resolution of nausea and vomiting and was able to tolerate improved oral intake. She was gradually weaned from D10 maintenance fluids as her oral intake and gastrointestinal symptoms improved on days 2-4 of hospitalization. Her daily protein intake was also gradually increased per sick-day diet protocol . Her neuOur case highlights multiple important aspects in the individualized treatment of mild COVID-19 infection in a patient with MSUD, a relatively uncommon inborn error of metabolism that can be exacerbated by injury or infection. The metabolic pathway affected by MSUD is demonstrated in Figure The effects of COVID-19 infection in patients with MSUD have only been documented in two prior publications ,7. The fOur case also brings up multiple important points regarding the unique pharmacologic treatment of our patient with MSUD during COVID-19 infection. As mentioned above, the patient’s immunocompromised state due to the medical management of her rheumatoid arthritis put her at an increased risk of developing a more severe COVID-19 course. For this reason, we decided to initiate remdesivir therapy with the goal of reducing the patient’s risk of progressing to more serious COVID-19 disease . HoweverAnother widely used pharmacotherapeutic agent in the treatment of COVID-19 in patients requiring supplemental oxygen is dexamethasone . The priThe treatment of COVID-19 infection in a patient with MSUD requires a unique approach. Special care should be placed on maintaining adequate oral intake and closely monitoring amino acid levels to prevent progression to a metabolic crisis, especially in the setting of gastrointestinal distress. If the patient develops COVID-19 pneumonia with an oxygen requirement, via invasive or noninvasive means, glucocorticoids such as dexamethasone should be avoided, as they could trigger a metabolic crisis. Instead, nonsteroid options such as remdesivir and baricitinib should be considered if the patient is able to tolerate the side effects.