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March 02 | Daily COVID-19 LST Report

Understanding the Pathology

· T cell lymphopenia may be more prevalent in symptomatic SARS-CoV-2 infections. A multidisciplinary group of infectious disease and immunology experts from the London School of Hygiene and Tropical Medicine conducted a systematic review of 61 articles on the T-cell immune response against SARS-CoV-2 in humans. They found T-cell peripheral lymphopenia (CD4+, CD8+) occurred more in symptomatic adults compared to children and asymptomatic adults, with a correlation between T cell lymphopenia and disease severity, duration of positivity, and mortality. Authors suggest T-cell responses to SARS-CoV-2 are complex and under-studied, and urge researchers to conduct further studies in asymptomatic patients and vaccine recipients.

Transmission & Prevention

· Outdoor settings continues to show decreased transmission. A systematic review of articles conducted at the University of California Berkeley by the Joint Medical Program that included 12 highly heterogeneous studies concerning outdoor transmission of viruses (5 studies with SARS-CoV-2; 7 studies with influenza or adenovirus) found that there is far lower transmission outdoors compared to indoors. However, without further study, risks may mitigate the benefits of resuming outdoor experiences without sufficient caution.

· COVID-19 emergency alert text messages may be effective in promoting the practice of preventive behaviors. Members of the Department of Public Health Sciences, in cooperation with local and central governments of South Korea, conducted a web-based survey of 990 participants about the association between alarm text messages and preventive behaviors during March 2020. They found 49.2% always read the alarm messages, and those who always read the messages were more likely to wear facial masks (β=.074, P=.01), avoid crowded place (β=.078, P=.01), and cancel social gatherings (β=.103, P<.001). Authors suggest that broadcasting public health information via text message is an effective strategy for disseminating important health information during the pandemic.

· Airborne dispersion of droplets during coughing correlates with distance. Investigators from the A*STAR Institute of High Performance Computing and Singapore General Hospital analyzed the transmission of viral particles by modeling the disbursement of droplets in the setting of a spontaneous indoor cough. They found the probability of droplet transmission decreased with increasing distance (0.5 vs 1 meter) from cougher to listener, use of facial covering, and increased relative humidity of 60%. This study highlights the importance of adherence to social distancing and mask wearing to aid in the decrease of SARS-CoV-2 transmission during the pandemic.


· Systematic review and patient-level meta-analysis shows SARS-CoV-2 viral dynamics are more amenable to treatments with antiviral therapies. Experts in infectious disease and immunology from University College London, among others, conducted a systematic review of 45 papers (645 patients) and used extracted data to generate models of viral load trajectories under different treatment protocols. They found faster viral clearance in patients treated with remdesivir (adjusted hazard ratio [AHR]: 9.19, p<0.001), interferon (AHR: 2.2, p=0.015), and interferon plus ribavirin (AHR: 6.04, p = 0.006) while older, male, and more severely ill patients had slower viral clearance. The authors suggest that early use of antivirals may play a significant role in altering viral trajectories and recommend clinical trials to corroborate their findings.

· In-hospital use of statins is associated with a reduced risk of mortality in COVID-19. Endocrinologists from Universitas Padjadjaran in Indonesia conducted a systematic review and meta-analysis of 13 articles investigating the effect of statins on mortality in 52,122 COVID-19 patients published before November 2020. They found in-hospital use of statins decreased mortality (RR 0.54, 95% CI 0.50–0.58, p<0.00001; I2: 0%, p = 0.87); pre-hospital chronic statin therapy had no effect (RR 1.18, 95% CI 0.79–1.77, p = 0.415; I2: 68.6%, p = 0.013). Authors suggest in-hospital use of statins may reduce of mortality risk among patients with COVID-19 though recognize limitations of the retrospective and non-randomized methodology included in this analysis.

Adjusting Practice During COVID-19

· How do you manage regional bone banks during a declaration of a state of emergency concerning COVID-19? Researchers from the Kitasato University School of Medicine Department of Orthopedic Surgery and the Kitasato University Bone Bank found that changes were needed in the management of the bone bank in order to prevent the transmission of COVID-19. They suggest screening donors and recipients for COVID-19 with PCR and implementation of biological inactivation methods, including heat treatment of bone grafts.

R&D: Diagnosis & Treatments

· Does famotidine reduce the risk of progression to severe disease, death, and intubation for COVID-19 patients? Internists and epidemiologists from several American and Chinese institutions conducted a systematic review and meta-analysis of five articles assessing the use of famotidine in COVID-19 patients. They found famotidine use produced no statistically significant effect in decreasing progression to severe disease, intubation, or death (RR: 0.82 [95% CI = 0.52–1.30], P = 0.40). Patients who received famotidine had lower reported median ferritin (P = 0.030), CRP (P = 0.002), and procalcitonin (P = 0.004) levels. Authors suggest though famotidine does not appear to decrease poor outcomes in COVID-19 patients, there still may be some potential benefit to its use given their observation of lower serum markers thought to be associated with COVID-19 prognosis.

· Diagnostic performance of COVID-19 serological assays during early infection may not be as helpful as later on. This systematic review and meta-analysis by researchers from the National University of Singapore analyzes the diagnostic performances of COVID-19 IgM and IgG serological assays during early infection in 55 studies with virologically confirmed SARS-CoV-2. Results showed the overall sensitivity and specificity to be 0.727 and 0.918 for IgM testing and 0.788 and 0.948 for IgG. They also found test accuracy significantly rose for both assays using enzyme-linked immunosorbent assay (ELISA) after Day 14. The authors conclude that because seroconversion of IgM and IgG were found to be low during the first week of infection (37.5% and 35.4%, respectively) and rose around Day 21 (81.3% and 93.3%, respectively), these assays are most practical later after symptom onset, and this understanding should be considered when choosing diagnostic testing for COVID-19.

· Early anti-SARS-CoV-2 immunoglobulin G response may be associated with disease severity in patients with COVID-19. A prospective study conducted at the Toho University School of Medicine in Tokyo, Japan found that 7 of 21 patients who tested positive by PCR produced an early SARS-CoV-2 IgG response. This response was associated with higher severity of disease, elevated CRP and D-dimer levels upon admission and higher respiratory rate and lower lymphocyte percentage on Day 7 of hospitalization compared to late SARS-CoV-2 IgG responders. It was also determined that early-IgG response was associated with lower viral load, which is contrary to previous studies that have associated increasing COVID-19 infection severity with higher viral load. These results suggest potential for early production of IgG to be used as a clinical indicator for disease severity, however further studies are needed to analyze and differentiate early vs. late IgG responses in regards to clinical presentation.

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