Multimodal Remote Home Monitoring of Lung Transplant Recipients during COVID-19 Vaccinations: Usability Pilot Study of the COVIDA Desk Incorporating Wearable Devices.

Background and Objectives: Remote patient monitoring (RPM) of vital signs and symptoms for lung transplant recipients (LTRs) has become increasingly relevant in many situations. Nevertheless, RPM research integrating multisensory home monitoring in LTRs is scarce. We developed a novel multisensory home monitoring device and tested it in the context of COVID-19 vaccinations. We hypothesize that multisensory RPM and smartphone-based questionnaire feedback on signs and symptoms will be well accepted among LTRs. To assess the usability and acceptability of a remote monitoring system consisting of wearable devices, including home spirometry and a smartphone-based questionnaire application for symptom and vital sign monitoring using wearable devices, during the first and second SARS-CoV-2 vaccination. Materials and Methods: Observational usability pilot study for six weeks of home monitoring with the COVIDA Desk for LTRs. During the first week after the vaccination, intensive monitoring was performed by recording data on physical activity, spirometry, temperature, pulse oximetry and self-reported symptoms, signs and additional measurements. During the subsequent days, the number of monitoring assessments was reduced. LTRs reported on their perceptions of the usability of the monitoring device through a purpose-designed questionnaire. Results: Ten LTRs planning to receive the first COVID-19 vaccinations were recruited. For the intensive monitoring study phase, LTRs recorded symptoms, signs and additional measurements. The most frequent adverse events reported were local pain, fatigue, sleep disturbance and headache. The duration of these symptoms was 5-8 days post-vaccination. Adherence to the main monitoring devices was high. LTRs rated usability as high. The majority were willing to continue monitoring. Conclusions: The COVIDA Desk showed favorable technical performance and was well accepted by the LTRs during the vaccination phase of the pandemic. The feasibility of the RPM system deployment was proven by the rapid recruitment uptake, technical performance (i.e., low number of errors), favorable user experience questionnaires and detailed individual user feedback.

COVID-Related Chronic Allograft Dysfunction in Lung Transplant Recipients: Long-Term Follow-up Results from Infections Occurring in the Pre-vaccination Era

Introduction: We report on characteristics and lung function outcomes among lung transplant recipients (LTRs) after COVID-19 with infections occurring in the first year of the coronavirus pandemic prior to introduction of the vaccines. Methods: This was a retrospective study of 18 LTRs who tested positive for SARS-CoV-2 between 1 February 2020 and 1 March 2021. The mean age was 49.9 (22–68) years;12 patients (67%) were male. Two patients died due to severe COVID-19. Results: During the study period, there were 18 lung transplant recipients with a community-acquired SARS-CoV-2 infection. In this cohort, seven had mild, nine had moderate, and two had severe COVID-19. All patients with mild and moderate COVID-19 survived, but the two patients with severe COVID-19 died in the intensive care unit while intubated and on mechanical ventilation. Most patients with moderate COVID-19 showed a permanent lung function decrease that did not improve after 12 months. Conclusion: A majority of LTRs in the current cohort did not experience an alteration in the trajectory of FEV1 evolution after developing SARS-CoV-2 infection. However, in the patients with moderate COVID-19, most patients had a decline in the FEV1 that was present after 1 month after recovery and did not improve or even deteriorated further after 12 months. In LTRs, COVID-19 can have long-lasting effects on pulmonary function. Treatment strategies that influence this trajectory are needed.

COVID-19-Associated Lung Fibrosis: Two Pathways and Two Phenotypes, Lung Transplantation, and Antifibrotics

COVID-19 can be associated with lung fibrosis. Although lung fibrosis after COVID-19 is a relatively rare finding, the mere fact that globally a very large number of patients have had COVID-19 leads to a significant burden of disease. However, patients with COVID-19-associated lung fibrosis have different clinical and radiological features. The aim of this review is to define the different phenotypes of COVID-19-associated lung fibrosis, based on the medical literature. We found that two phenotypes have emerged. One phenotype is COVID-19-related acute respiratory distress syndrome (CARDS);the other phenotype is post-COVID-19 pulmonary fibrosis (PCPF). Both phenotypes have different risk factors, clinical, and radiological features, and differ in their pathophysiological mechanisms and prognoses. A long-term follow-up of patients with pulmonary complications after COVID-19 is warranted, even in patients with only discrete fibrosis. Further studies are needed to determine the optimal treatment because currently the literature is scarce, and evidence is only based on small case series or case reports.

COVID-19-related end stage lung disease: two distinct phenotypes.

In COVID-19 related end stage lung disease, there are two distinct phenotypes. The first phenotype is the COVID-19 related acute respiratory distress syndrome (CARDS) showing a classical histopathological pattern of fibrotic diffuse alveolar damage (DAD). The second phenotype is the post-COVID pulmonary fibrosis (PCPF), in which the diagnosis is based on the combined clinical, radiological and (if available) pathological information. Both phenotypes have different clinical features, risk factors, biomarkers and pathophysiology. The exact prognosis in these two phenotypes as well as optimal treatment needs further studies.Key messagesTwo different phenotypes exist for COVID-19 related pulmonary fibrosis. The CARDS phenotype has a worse prognosis compared to the PCPF phenotype, which requires longer-term follow-up and evolves without ARDS picture. The best treatment options for the two different phenotypes, such as anti-fibrotic drugs or lung transplantation, still needs to be defined in future studies.

Clinical Characteristics, Treatments and Outcomes of 18 Lung Transplant Recipients with COVID-19

We report clinical features, treatments and outcomes in 18 lung transplant recipients with laboratory confirmed SARS-CoV-2 infection. We performed a single center, retrospective case series study of lung transplant recipients, who tested positive for SARS-CoV-2 between 1 February 2020 and 1 March 2021. Clinical, laboratory and radiology findingswere obtained. Treatment regimens and patient outcome data were obtained by reviewing the electronic medical record. Mean age was 49.9 (22–68) years, and twelve (67%) patients were male. The most common symptoms were fever (n = 9, 50%), nausea/vomiting (n = 7, 39%), cough (n = 6, 33%), dyspnea (n = 6, 33%) and fatigue (n = 6, 33%). Headache was reported by five patients (28%). The most notable laboratory findings were elevated levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH). Computed Tomography (CT) of the chest was performed in all hospitalized patients (n = 11, 7%), and showed ground-glass opacities (GGO) in 11 patients (100%), of whom nine (82%) had GGO combined with pulmonary consolidations. Six (33%) patients received remdesivir, five (28%) intravenous dexamethasone either alone or in combination with remdesivir, and 15 (83%) were treated with broad spectrum antibiotics including co-amoxicillin, tazobactam-piperacillin and meropenem. Four (22%) patients were transferred to the intensive care unit, two patients (11%) required invasive mechanical ventilation who could not be successfully extubated and died. Eighty-nine percent of our patients survived COVID-19 and were cured. Two patients with severe COVID-19 did not survive.

Calcineurin inhibitors revisited: A new paradigm for COVID-19?

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can cause mild, moderate or severe disease (COVID-19). In severe disease, there is hyperinflammation causing severe symptoms. Severe COVID-19 is an immunological phenomenon, rather than a direct viral damage disease. Therapies for COVID-19 are all investigational therapies. In case of severe disease, treatment with a calcineurin inhibitor could be promising. In this article we explain the mechanisms of calcineurin inhibitor treatment for COVID-19, based on experiences seen in solid organ transplant recipients who suffered from COVID-19.

Transplant Drugs against SARS, MERS and COVID-19

There is an urgent need to develop drugs and vaccines to counteract the effects of the new coronavirus SARS-CoV-2 and adequately treat the corona virus disease (COVID-19). As these drugs are still under investigation, research also focuses on existing medication with proven effectiveness in other coronaviral diseases. The advantages of existing therapeutic drugs that are currently approved (for other indications) are the known safety profile, general availability and relatively lower costs involved in extending the purpose to a new disease. Calcineurin inhibitors (CNI) are drugs that have shown effectiveness in several coronaviral diseases, and are well-known and widely used drugs in transplant medicine. The aim of this narrative review is to present the current evidence of CNI in coronaviral diseases, the biophysiology of CNI and to suggest possible ways to study CNI as a new treatment option for COVID-19. We searched original papers, observational studies, case reports, and meta-analyses published between 2000 and 2020 in English in the PubMed database and Google Scholar using the keywords: (coronavirus), (treatment), (MERS), (SARS), (COVID-19), (tacrolimus), (ciclosporin), (cyclosporin) AND (calcineurin inhibitor). We excluded studies in patients with clear indications for immunosuppressive therapy. Additionally, we searched in the preprint servers and the World Health Organization bulletin. Ten studies were identified and included. Calcineurin inhibitor therapy has been suggested to be effective for coronaviral diseases in different settings. The results are summarized in a table. CNI should be investigated as a first treatment option based on evidence of direct antiviral effects and its properties preventing severe systemic hyperinflammation, as has been observed in COVID-19 with predominantly pulmonary immunopathological changes.

Calcineurin inhibitors revisited: A new paradigm for COVID-19?

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can cause mild, moderate or severe disease (COVID-19). In severe disease, there is hyperinflammation causing severe symptoms. Severe COVID-19 is an immunological phenomenon, rather than a direct viral damage disease. Therapies for COVID-19 are all investigational therapies. In case of severe disease, treatment with a calcineurin inhibitor could be promising. In this article we explain the mechanisms of calcineurin inhibitor treatment for COVID-19, based on experiences seen in solid organ transplant recipients who suffered from COVID-19.

COVID-19 in Patients with Solid Organ Transplantation: A Systematic Review

The novel coronavirus, SARS-CoV-2, is causing a pandemic of unknown precedent, with huge healthcare challenges and worldwide disruptions to economic and social life. Lung transplant recipients and other solid organ transplant (SOT) recipients are immunosuppressed, and therefore are generally considered at an increased risk for severe infections. Given the current gap in knowledge and evidence regarding the best management of these patients, we conducted a systematic review of studies on SARS-CoV-2 infections and Coronavirus Disease 2019 (COVID-19) in SOT recipients, to evaluate the association between immunosuppression in these patients, SARS-CoV-2 infection and COVID-19 outcomes. The focus was the severity of the disease, the need for mechanical ventilation and intensive care unit (ICU) admissions, and rate of death. The literature search was conducted repeatedly between 16 March and 8 April 2020. We searched original papers, observational studies, case reports, and meta-analyses published between 2019 and 2020 using two databases (PubMed, Google Scholar) with the search terms: [transplant OR immunosuppression] AND [COVID-19 OR SARS-CoV-2]. Further inclusion criteria were publications in English, French, German and Italian, and reference to humans. We also searched the reference lists of the studies encountered. From an initial search of PubMed and Google Scholar, 19 potential articles were retrieved, of which 14 were excluded after full-text screening (not being case reports or case series), leaving 5 studies for inclusion. No further studies were identified from the bibliographies of retrieved articles. Based on the limited research, no firm conclusions can be made concerning SOT recipients, but the current evidence suggests that immunosuppression is most likely associated with a better outcome of SARS-CoV-2 infection and COVID-19 because it prevents hyperinflammation (cytokine storm) in this particular population. There is a need for further research that would allow results to be adjusted for other factors potentially impacting COVID-19 severity and outcome.