• Accelerating Development of SARS-CoV-2 Vaccines — The Role for Controlled Human Infection Models

      Deming, M.E.; Michael, N.L.; Neuzil, K.M. (Massachusetts Medical Society, 2020-07-01)
    • Airborne transmission of SARS-CoV-2

      Prather, Kimberly A; Marr, Linsey C; Schooley, Robert T; McDiarmid, Melissa A; Wilson, Mary E; Milton, Donald K (American Association for the Advancement of Science, 2020-10-05)
    • Analysis of antibody responses after COVID-19 vaccination in liver transplant recipients and those with chronic liver diseases

      Thuluvath, Paul J; Robarts, Polly; Chauhan, Mahak (Elsevier Inc., 2021-08-26)
      Background & Aims: Liver transplant (LT) recipients or other immunocompromised patients were not included in the registration trials of vaccine studies against SARS-CoV-2. Although clinical efficacy of COVID vaccines in immunocompromised patients was unknown, many societies had recommended vaccination of this highly vulnerable patient population. Methods: In this prospective study, we determined antibody (Ab) response to spike protein, 4 weeks after the 2nd dose of mRNA vaccines or after the single dose of Johnson & Johnson vaccine, in LT recipients and those with chronic liver diseases (CLD) with and without cirrhosis. Results: Of the 233 patients enrolled so far, 62 had LT, 79 had cirrhosis (10 decompensated) and 92 had CLD without cirrhosis. Ab titers were defined as undetectable (<0.40 U/mL), suboptimal (0.40 - 250 U/mL) and adequate (>250 U/mL). Of the 62 patients who had LT, Ab levels were undetectable in 11 patients and suboptimal (median titer 17.6, range 0.47 - 212 U/mL) in 27 patients. Among 79 patients with cirrhosis, 3 had undetectable Ab and 15 had suboptimal (median titer 41.3, range 0.49 - 221 U/L) response. Of the 92 patients without cirrhosis, four had undetectable Ab and 19 had suboptimal (median titer 95.5, range 4.9 - 234 U/L) Ab response. Liver transplantation, use of 2 or more immunosuppression medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor immune response on multivariable analysis. No patient had any serious adverse events. Conclusions: Poor antibody response after SARS-CoV-2 vaccination was seen in 61% of LT recipients and 24% of those with CLD.
    • Anti-SARS-CoV-2 immune responses in patients receiving an allogeneic stem cell or organ transplant

      Atanackovic, Djordje; Luetkens, Tim; Avila, Stephanie V.; Hardy, Nancy M.; Lutfi, Forat; Sanchez-Petitto, Gabriela; Mause, Erica Vander; Glynn, Nicole; Mannuel, Heather D.; Alkhaldi, Hanan; et al. (MDPI AG, 2021-07-03)
      Patients after autologous (autoSCT) and allogeneic stem cell transplantation (alloSCT) are at an increased risk of COVID-19-related morbidity and mortality, compounded by an immune system weakened by the underlying malignancy and prior treatments. Allogeneic transplantation, including stem cell and solid organ transplants, requires intensive immunosuppressive prophylaxis, which may further undermine the development of a protective vaccine-induced anti-viral immunity. Herein, we report on short- and long-term antiviral immune responses in two peri-stem cell transplant recipients and a third patient who received a COVID-19 vaccination after kidney transplantation. Our data indicate that: (1) patients post-alloSCT may be able to mount an anti-COVID-19 immune response; however, a sufficient time interval between transplant and exposure may be of critical importance; (2) alloSCT recipients with preexisting anti-SARS-CoV-2 immunity are at risk for losing protective humoral immunity following transplantation, particularly if the stem-cell donor lacks antiviral immunity, e.g., vaccine-derived immunity; and (3) some post-transplant patients are completely unable to build an immune response to a COVID-19 vaccine, perhaps based on the prophylactic suppression of T cell immunity.
    • Biological and Psychological Factors Determining Neuropsychiatric Outcomes in COVID-19

      Tizenberg, Boris N; Brenner, Lisa A; Lowry, Christopher A; Okusaga, Olaoluwa O; Benavides, David R; Hoisington, Andrew J; Benros, Michael E; Stiller, John W; Kessler, Ronald C; Postolache, Teodor T (Springer Nature, 2021-10-01)
      Purpose of Review: We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology. Recent Findings: Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem. Most common psychiatric manifestations include delirium, mood disorders, anxiety disorders, and posttraumatic stress disorder. “Long-COVID” non-syndromal presentations include “brain-fogginess,” autonomic instability, fatigue, and insomnia. Summary: SARS-CoV-2 infection can trigger prior vulnerabilities based on the priming of microglia and other cells, induced or perpetuated by aging and mental and physical illnesses. COVID-19 could further induce priming of neuroimmunological substrates leading to exacerbated immune response and autoimmunity targeting structures in the central nervous system (CNS), in response to minor immune activating environmental exposures, including stress, minor infections, allergens, pollutants, and traumatic brain injury. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
    • A Brief Update on the Effect of the COVID-19 Pandemic on Hip and Knee Arthroplasty Patients in the United States: A Multicenter Update to a Previous Survey Study of Patients Postponed by the Pandemic

      Brown, Timothy S; Bedard, Nicholas A; Rojas, Edward O; Anthony, Christopher A; Schwarzkopf, Ran; Stambough, Jeffrey B; Nandi, Sumon; Prieto, Hernan; Parvizi, Javad; Bini, Stefano A; et al. (Elsevier Inc., 2020-12-03)
      Background: In March 2020, elective total hip and knee arthroplasty (THA and TKA) were suspended across the United States in response to the COVID-19 pandemic. We had previously published the results of a survey to the affected patients from 6 institutions. We now present the results of a larger distribution of this survey, through May and June 2020, to electively scheduled patients representing different regions of the United States. Methods: Fifteen centers identified through the American Association of Hip and Knee Surgeons Research Committee participated in a survey study of THA and TKA patients. Patients scheduled for primary elective THA or TKA but canceled due to the COVID-19 elective surgery stoppage (3/2020-5/2020) were included in the study. Descriptive statistics along with subgroup analysis with Wilcoxon rank were performed. Results: In total, surveys were distributed to 2135 patients and completed by 848 patients (40%) from 15 institutions. Most patients (728/848, 86%) had their surgery postponed or canceled by the surgeon or hospital. Unknown length of surgical delay remained the highest source of anxiety among survey participants. Male patients were more likely to be willing to proceed with surgery in spite of COVID-19. There were minimal regional differences in responses. Only 61 patients (7%) stated they will continue to delay surgery for fear of contracting COVID-19 while in the hospital. Conclusion: Similar to the previous study, the most anxiety-provoking thought was the uncertainty, over if and when the canceled joint replacement surgery could be rescheduled. Patients suffering from the daily pain of hip and knee arthritis who have been scheduled for elective arthroplasty remain eager to have their operation as soon as elective surgery is allowed to resume.
    • Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 and SARS-CoV

      Weston, Stuart; Coleman, Christopher M; Haupt, Robert; Logue, James; Matthews, Krystal; Li, Yize; Reyes, Hanako M; Weiss, Susan R; Frieman, Matthew B (American Society for Microbiology, 2020-10-14)
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and has rapidly caused a pandemic, with over 20 million recorded COVID-19 cases in August 2020 (https://covid19.who.int/). There are no FDA-approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA-approved drugs. Rapid development and human testing of potential antivirals is urgently needed. Numerous drugs are already approved for human use, and subsequently, there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that 17 of these inhibit SARS-CoV-2 at non-cytotoxic concentrations. We directly followed up seven of these to demonstrate that all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found that both drugs protect mice from clinical disease.IMPORTANCE There are no FDA-approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly repurposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV in vitro We found that 17 of these inhibit SARS-CoV-2, suggesting that they may have pan-anti-coronaviral activity. We directly followed up seven of these and found that they all inhibit infectious-SARS-CoV-2 production. Moreover, we evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We found that neither drug inhibited viral replication in the lungs, but both protected against clinical disease.
    • Comparison of sars-cov-2 receptors expression in primary endothelial cells and retinoic acid-differentiated human neuronal cells

      Benedetti, Francesca; Silvestri, Giovannino; Mavian, Carla; Weichseldorfer, Matthew; Munawwar, Arshi; Cash, Melanie N.; Dulcey, Melissa; Vittor, Amy Y.; Ciccozzi, Massimo; Salemi, Marco; et al. (MDPI AG, 2021-10-30)
      SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is primarily responsible for coronavirus disease (COVID-19) and it is characterized by respiratory illness with fever and dyspnea. Severe vascular problems and several other manifestations, including neurological ones, have also been frequently reported, particularly in the great majority of “long hauler” patients. SARS-CoV-2 infects and replicates in lung epithelial cells, while dysfunction of endothelial and neuronal brain cells has been observed in the absence of productive infection. It has been shown that the Spike protein can interact with specific cellular receptors, supporting both viral entry and cellular dysfunction. It is thus clear that understanding how and when these receptors are regulated, as well as how much they are expressed would help in unveiling the multifaceted aspects of this disease. Here, we show that SH-SY5Y neuroblastoma cells express three important cellular surface molecules that interact with the Spike protein, namely ACE2, TMPRSS2, and NRP1. Their levels increase when cells are treated with retinoic acid (RA), a commonly used agent known to promote differentiation. This increase matched the higher levels of receptors observed on HUVEC (primary human umbilical vein endothelial cells). We also show by confocal imaging that replication-defective pseudoviruses carrying the SARS-CoV-2 Spike protein can infect differentiated and undifferentiated SH-SY5Y, and HUVEC cells, although with different efficiencies. Neuronal cells and endothelial cells are potential targets for SARS-CoV-2 infection and the interaction of the Spike viral protein with these cells may cause their dysregulation. Characterizing RNA and protein expression tempo, mode, and levels of different SARS-CoV-2 receptors on both cell subpopulations may have clinical relevance for the diagnosis and treatment of COVID-19-infected subjects, including long hauler patients with neurological manifestations. © 2021 by the authors.
    • Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection

      Rathnasinghe, Raveen; Strohmeier, Shirin; Amanat, Fatima; Gillespie, Virginia L; Krammer, Florian; García-Sastre, Adolfo; Coughlan, Lynda; Schotsaert, Michael; Uccellini, Melissa B (Springer Nature, 2020-11-06)
      Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2) [1-3]. Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in the nasal turbinates, lung and brain, with high lethality, and cytokine/chemokine production. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the nasal turbinates and lung, and no clinical signs of infection. The K18-hACE2 model provides a stringent model for testing vaccines and antivirals, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains.
    • Concurrent COVID-19 and Pneumocystis jirovecii pneumonia in a severely immunocompromised 25-year-old patient.

      Bhat, Pavan; Noval, Mandee; Doub, James B; Heil, Emily (Elsevier Inc., 2020-08-05)
    • Coronavirus interactions with the cellular autophagy machinery

      Miller, Katelyn; McGrath, Marisa E.; Hu, Zhiqiang; Ariannejad, Sohha; Weston, Stuart; Frieman, Matthew; Jackson, William T. (Taylor and Francis Inc., 2020-09-23)
      The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is the most recent example of an emergent coronavirus that poses a significant threat to human health. Virus-host interactions play a major role in the viral life cycle and disease pathogenesis, and cellular pathways such as macroautophagy/autophagy prove to be either detrimental or beneficial to viral replication and maturation. Here, we describe the literature over the past twenty years describing autophagy-coronavirus interactions. There is evidence that many coronaviruses induce autophagy, although some of these viruses halt the progression of the pathway prior to autophagic degradation. In contrast, other coronaviruses usurp components of the autophagy pathway in a non-canonical fashion. Cataloging these virus-host interactions is crucial for understanding disease pathogenesis, especially with the global challenge of SARS-CoV-2 and COVID-19. With the recognition of autophagy inhibitors, including the controversial drug chloroquine, as possible treatments for COVID-19, understanding how autophagy affects the virus will be critical going forward. Abbreviations: 3-MA: 3-methyladenine (autophagy inhibitor); AKT/protein kinase B: AKT serine/threonine kinase; ATG: autophagy related; ATPase: adenosine triphosphatase; BMM: bone marrow macrophage; CGAS: cyclic GMP-AMP synthase; CHO: Chinese hamster ovary/cell line; CoV: coronaviruses; COVID-19: Coronavirus disease 2019; DMV: double-membrane vesicle; EAV: equine arteritis virus; EDEM1: ER degradation enhancing alpha-mannosidase like protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; GFP: green fluorescent protein; HCoV: human coronavirus; HIV: human immunodeficiency virus; HSV: herpes simplex virus; IBV: infectious bronchitis virus; IFN: interferon; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCoV: mouse coronavirus; MERS-CoV: Middle East respiratory syndrome coronavirus; MHV: mouse hepatitis virus; NBR1: NBR1 autophagy cargo receptor; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2 (autophagy receptor that directs cargo to phagophores); nsp: non-structural protein; OS9: OS9 endoplasmic reticulum lectin; PEDV: porcine epidemic diarrhea virus; PtdIns3K: class III phosphatidylinositol 3-kinase; PLP: papain-like protease; pMEF: primary mouse embryonic fibroblasts; SARS-CoV: severe acute respiratory syndrome coronavirus; SKP2: S-phase kinase associated protein 2; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; ULK1: unc-51 like autophagy activating kinase 1; Vps: vacuolar protein sorting.
    • COVID-19 and Lessons to be Learned from Prior Coronavirus Outbreaks

      Deming, M.E.; Chen, W.H. (American Thoracic Society, 2020)
      Coronaviruses are large RNA viruses that are endemic among bats globally. These bat viruses are known to readily recombine and present an ever-present potential to jump host species, allowing for emergence into novel hosts.[1] Four seasonal human coronaviruses (hCoV) circulate yearly as mild “common cold” viruses causing upper respiratory symptoms: OC43, HKU1, NL63, and 229E. Additionally, three novel coronaviruses have emerged as zoonotic human infections in the past 17 years. SARS-coronavirus (SARS-CoV), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and the 2019 novel coronavirus (SARS-CoV-2)[2] have each been associated with lower respiratory symptoms, progressing in a subset of individuals to acute respiratory distress syndrome (ARDS) and death.
    • COVID-19 and Solid Organ Transplantation: A Review Article.

      Azzi, Yorg; Bartash, Rachel; Scalea, Joseph; Loarte-Campos, Pablo; Akalin, Enver (Wolters Kluwer Health, 2021-01)
      The coronavirus pandemic has significantly impacted solid organ transplantation (SOT). Early in the outbreak period, transplant societies recommended suspending living kidney transplant programs in communities with widespread transmission to avoid exposing recipients to increased risk of immunosuppression, while recommendations were made to reserve deceased-donor kidney transplantation for likely life-saving indications. SOT recipients may be at high risk from COVID-19 disease due to chronic immunosuppressive treatment and other medical comorbidities. Mortality rates reported between 13 to over 30% in SOT recipients. In addition to high rates of complications and mortality attributable to COVID-19 infections, the pandemic has also led to additional complexities in transplantation including new questions regarding screening of donors and recipients, decision making to accept a patient for kidney transplant or wait after pandemic. The clinical implications of COVID-19 infection may also differ depending on the type of the transplanted organ and recipient comorbidities which further impacts decisions on continuing transplantation during the pandemic. Transplant activity during a pandemic should be tailored with careful selection of both donors and recipients. Furthermore, while tremendous strides have been made in treatment strategies and vaccinations, the impact of these in transplant recipients may be attenuated in the setting of their immunosuppression. In this review, we aim to summarize several aspects of COVID-19 in transplantation, including the immune response to SARS-CoV-2, SARS-CoV-2 diagnostics, clinical outcomes in SOT recipients, and end-stage kidney disease patients, transplant activity during the pandemic, and treatment options for COVID-19 disease.
    • COVID-19: Knowns, Unknowns, and Questions

      Weston, S.; Frieman, M.B. (American Society for Microbiology, 2020)
      The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months highlights the transmissibility of this family of viruses and the significant morbidity and mortality that they can cause. We highlight the current state of knowledge of coronavirus biology while answering questions concerning the current outbreak of SARS-CoV-2. Copyright 2020 Weston and Frieman.
    • Delayed Spontaneous Bilateral Pneumothorax in a Previously Healthy Nonventilated COVID-19 Patient

      Huis In 't Veld, Maite A; Ten Kortenaar, Suzanne W; Bodifee, Thomas M; Stavast, Jeroen; Kessels, Bart (Elsevier Inc., 2021-01-22)
      Background: The novel coronavirus disease 2019 (COVID-19) is a recent viral outbreak that has rapidly spread to multiple countries worldwide. Little is known about COVID-19 infection-related complications. Case Report: We report a patient who developed spontaneous bilateral pneumothorax after a recent COVID-19 infection. To our knowledge, this is the first reported case of spontaneous bilateral pneumothorax in a patient with recent confirmed severe acute respiratory syndrome coronavirus-2 infection without any risk factors for pneumothorax and who had not received positive pressure ventilation. Why Should an Emergency Physician Be Aware of This?: There may be a possible correlation between a recent COVID-19 infection and the development of spontaneous pneumothorax. The diagnosis of spontaneous pneumothorax should be considered in any patient with known or suspected recent COVID-19 infection who presents with new acute symptoms consistent with pneumothorax or sudden clinical deterioration.
    • Detection and Differentiation of SARS-CoV-2, Influenza, and Respiratory Syncytial Viruses by CRISPR

      Zhou, Huifen; Tsou, Jen-Hui; Chinthalapally, Molangur; Liu, Hongjie; Jiang, Feng (MDPI AG, 2021-05-01)
      SARS-CoV-2, influenza, and respiratory syncytial viruses (RSVs) cause acute respiratory infections with similar symptoms. Since the treatments and outcomes of these infections are different, the early detection and accurate differentiation of the viruses are clinically important for the prevention and treatment of the diseases. We previously demonstrated that clustered regularly interspaced short palindromic repeats (CRISPR) could rapidly and precisely detect SARS-CoV-2. The objective of this study was to develop CRISPR as a test for simultaneously detecting and accurately distinguishing the viruses. The CRISPR assay with an RNA guide against each virus was performed in the reference standards of SARS-CoV-2, influenza A and B, and RSV. The CRISPR assay had a limit of detection of 1–100 copies/µL for specifically detecting SARS-CoV-2, influenza A and B, and RSV without cross-reaction with other respiratory viruses. The validation of the test in nasopharyngeal specimens showed that it had a 90–100% sensitivity and 100% specificity for the detection of SARS-CoV-2, influenza A and B, and RSV. The CRISPR assay could potentially be used for sensitive detection and specific differentiation of the respiratory viruses. © 2021 by the authors.
    • Drosophila, a powerful model to study virus-host interactions and pathogenicity in the fight against SARS-CoV-2

      van de Leemput, Joyce; Han, Zhe (Springer Nature, 2021-06-13)
      The COVID-19 pandemic is having a tremendous impact on humanity. Although COVID-19 vaccines are showing promising results, they are not 100% effective and resistant mutant SARS-CoV-2 strains are on the rise. To successfully fight against SARS-CoV-2 and prepare for future coronavirus outbreaks, it is essential to understand SARS-CoV-2 protein functions, their host interactions, and how these processes convey pathogenicity at host tissue, organ and systemic levels. In vitro models are valuable but lack the physiological context of a whole organism. Current animal models for SARS-CoV-2 research are exclusively mammals, with the intrinsic limitations of long reproduction times, few progeny, ethical concerns and high maintenance costs. These limitations make them unsuitable for rapid functional investigations of virus proteins as well as genetic and pharmacological screens. Remarkably, 90% of the SARS-CoV-2 virus-host interacting proteins are conserved between Drosophila and humans. As a well-established model system for studying human diseases, the fruit fly offers a highly complementary alternative to current mammalian models for SARS-CoV-2 research, from investigating virus protein function to developing targeted drugs. Herein, we review Drosophila's track record in studying human viruses and discuss the advantages and limitations of using fruit flies for SARS-CoV-2 research. We also review studies that already used Drosophila to investigate SARS-CoV-2 protein pathogenicity and their damaging effects in COVID-19 relevant tissues, as well as studies in which the fly was used as an efficient whole animal drug testing platform for targeted therapeutics against SARS-CoV-2 proteins or their host interacting pathways.
    • Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination.

      Widge, Alicia T; Rouphael, Nadine G; Jackson, Lisa A; Anderson, Evan J; Roberts, Paul C; Makhene, Mamodikoe; Chappell, James D; Denison, Mark R; Stevens, Laura J; Pruijssers, Andrea J; et al. (Massachusetts Medical Society, 2020-12-03)
    • Effect of SARS-CoV-2 infection in pregnancy on maternal and neonatal outcomes in Africa: An AFREhealth call for evidence through multicountry research collaboration

      Nachega, Jean B.; Sam-Agudu, Nadia A.; Budhram, Samantha; Taha, Taha E.; Vannevel, Valerie; Somapillay, Priya; Ishoso, Daniel Katuashi; Pipo, Michel Tshiasuma; Nswe, Christian Bongo Pasi; Ditekemena, John; et al. (American Society of Tropical Medicine and Hygiene, 2021-02-01)
      In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health's COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa.
    • The Effect of the COVID-19 Pandemic on Hip and Knee Arthroplasty Patients in the United States: A Multicenter Update to the Previous Survey

      Brown, T.S.; Bedard, N.A.; Rojas, E.O.; Anthony, C.A.; Schwarzkopf, R.; Stambough, J.B.; Nandi, S.; Prieto, H.; Parvizi, J.; Bini, S.A.; et al. (Elsevier Inc., 2020-12-03)
      Background: In March 2020, elective total hip and knee arthroplasty (THA and TKA) were suspended across the United States in response to the COVID-19 pandemic. We had previously published the results of a survey to the affected patients from 6 institutions. We now present the results of a larger distribution of this survey, through May and June 2020, to electively scheduled patients representing different regions of the United States. Methods: Fifteen centers identified through the American Association of Hip and Knee Surgeons Research Committee participated in a survey study of THA and TKA patients. Patients scheduled for primary elective THA or TKA but canceled due to the COVID-19 elective surgery stoppage (3/2020-5/2020) were included in the study. Descriptive statistics along with subgroup analysis with Wilcoxon rank were performed. Results: In total, surveys were distributed to 2135 patients and completed by 848 patients (40%) from 15 institutions. Most patients (728/848, 86%) had their surgery postponed or canceled by the surgeon or hospital. Unknown length of surgical delay remained the highest source of anxiety among survey participants. Male patients were more likely to be willing to proceed with surgery in spite of COVID-19. There were minimal regional differences in responses. Only 61 patients (7%) stated they will continue to delay surgery for fear of contracting COVID-19 while in the hospital. Conclusion: Similar to the previous study, the most anxiety-provoking thought was the uncertainty, over if and when the canceled joint replacement surgery could be rescheduled. Patients suffering from the daily pain of hip and knee arthritis who have been scheduled for elective arthroplasty remain eager to have their operation as soon as elective surgery is allowed to resume. Copyright 2021