Pain, fatigue and psychological sequelae in patients surviving COVID-19: results from a prospective observational controlled study

Background: Since the beginning of the COVID-19 pandemic, there has been a growing recognition of its psychiatric implications. Anxiety, stress and sleep disorders are the main issues faced by healthcare professionals but less is known on the general population. We sought to determine the prevalence of neuro-psychiatric disorders, pain and fatigue in COVID-19 patients compared to healthy controls. The secondary outcome was to define the determinants of such disorders. Method(s): This single centre, prospective, observational, cohort study enrolled adult patients referring to the postCOVID-19 outpatient clinic of our University hospital from January 2021 to June 2021. Anthropometrical and functional respiratory data were collected, pain and fatigue were evaluated through a VAS scale while stress, anxiety, quality of sleep and the impact of the event were evaluated through questionnaires: perceived stress scale, ZUNG 1971, Pittsburgh and impact of events scale. Result(s): 301 cases and 115 controls were enrolled. The COVID-19 group had a higher prevalence of stress (scale points 18 vs 3, p<0.01), anxiety (ZUNG score 39 vs 21, p<0.01), and poor sleep (68.1% vs 6.1%, p<0.01). Alongside they had a significantly higher VAS pain score (2 vs 0, p<0.001) and VAS fatigue (3 vs 0, p<0.001). Female gender was the only feature that could predict fatigue, pain, anxiety, poor sleep quality and post-traumatic stress disorder syndrome. COVID-19 severity wasn't associated with any psichological sequelae. Conclusion(s): In an outpatient setting, stress, anxiety, sleep quality, pain and fatigue should be assessed in the holistic view of post-COVID-19 patients, especially in females.

Could biological disease modifying anti rheumatic drugs (bDMARDs) and small molecules have a key role in preventing COVID-19 infection?

Background: The clinical manifestations of COVID-19 infection are very heterogeneous. Rheumatic patients should be more susceptible to develop severe forms of COVID-19 pneumonia due to an unbalanced immune response and treatment immunodepressants (disease modifying anti rheumatic drugs-DMARDs). Aims and objectives: To investigate if the chronic use of biological DMARDs and small molecules may increase the susceptibility to COVID-19 and to developing severe disease. Method(s): We studied 43 consecutive patients on bDMARDs or small molecules from March 2020 to January 2022. Data collection included: rheumatic diagnosis, comorbidities, smoking history and COVID-19 clinical course according to MEWS (modifying early warning score) in 4 stages: 0=no symptoms at all;no hospitalization;1=not complicated disease with mild or non-specific symptoms;no hospitalization;2=mild pneumonia with clinical and/or radiological diagnosis, without any signs of severity;no hospitalization;3=severe pneumonia with respiratory failure with need of hospitalization;4=hospitalization in ICU or sub-ICU. Result(s): 30 patients (69.8%) got COVID infection: 26 were not hospitalized (MEWS 0=3.3%;1=70%;2=13.3%);of the four patients that required hospitalization, none was intubated. Hospitalized patients were obese and had hypertension, and 3 had a positive smoking history. Patients taking TNF-inhibitors compared to other treatment were not at major risk of COVID-19 infection (p=0.041). Conclusion(s): Rheumatic patients taking bDMARDs or small molecules appear more susceptible to contract SARSCoV-2 infection, but the development of severe forms appears to be rare.

CPAP-associated changes in oxygenation and clinical outcomes in severe COVID-19 pneumonia

Background: Continuous positive airway pressure (CPAP) can improve oxygenation in severe COVID-19 pneumonia. Objective(s): To assess whether CPAP-associated improvements in oxygenation can inform clinical outcomes in patients with severe COVID-19 pneumonia. Method(s): Retrospective study in patients with severe COVID-19 pneumonia treated with CPAP in three academic respiratory units in Milan, Italy. Arterial gas analysis obtained before and 1 hour after starting CPAP. CPAP failure defined as either death in the respiratory units while on CPAP or need for intubation. Result(s): 211 patients (mean age 64 years, 74% males) were included. Baseline median PaO2was 68 (57-83) mmHg, PaO2/FiO2(P/F) ratio was 129 (91-179) mmHg and alveolar-arterial (A-a) O2 gradient was 310 (177-559) mmHg. On CPAP, PaO2and P/F increased to 100 (79-141) (p<0.001) and 195 (132-257;p<0.001) mmHg and A-a gradient decreased to 240 (188-308;p<0.001) mmHg. 42 (19.9%) patients died in the respiratory units while on CPAP and 51 (24.2%) required intubation. There was a substantial overlap of baseline and CPAP-associated values of PaO2, P/F ratio and A-a gradient in CPAP failures and successes (Figure). CPAP-associated changes in PaO2, P/F ratio and A-a gradient in both groups were similar. Conclusion(s): CPAP-associated improvements in oxygenation cannot be used to inform clinical outcomes of the individual patient with severe COVID-19 pneumonia.

Oxidative stress and viral Infections: rationale, experiences, and perspectives on N-acetylcysteine.

This article explores current evidence on the role of oxidative stress in viral infections, and on the use of antioxidant drugs as adjunctive treatment. MEDLINE/PubMed was searched for appropriate keywords, and preclinical and clinical studies with reviews were retrieved and examined by authors. Old and current evidence shows that GSH content reduction is the main mechanism of redox imbalance in viral-infected cells. Clinical studies found that GSH levels are depleted in patients with viral infections such as HIV and SARS-CoV. Viral infections activate inflammation through different pathways, and several of these mechanisms are related to oxidative stress. NAC is a precursor of GSH, and many of its intracellular effects are mediated by GSH replenishment, but it also activates some anti-inflammatory mechanisms. NAC has an excellent safety profile and better oral and topical bioavailability than GSH. These characteristics make NAC a suitable option as a repurposed drug. Adjunctive antioxidant treatment may improve the outcomes of antiviral therapies. Current evidence supports the rationale for this practice and some clinical experience showed encouraging results.

Helmet CPAP treatment in patients with COVID-19 pneumonia: a multicentre cohort study

To evaluate outcomes of COVID-19 patients with pneumonia-related hypoxaemic acute respiratory failure (hARF) undergoing continuous positive airway pressure therapy (CPAP) treatment, hence, a multicentre, observational, prospective study was conducted between 7 March 2020 and 21 April 2020 in three high-dependency units (HDU) at two hospitals in Milan, Italy. The primary outcome was CPAP failure defined as the occurrence of either intubation or death due to any cause during hospital high-dependency units (HDU) stay while secondary outcomes included the weaning from CPAP to oxygen therapy (CPAP success), all-cause in-hospital and 30-day mortality. A total of 157 patients with hARF (median (IQR) PaO2/FIO2 ratio 142.9 (96.7-203.2)) underwent helmet CPAP with an initial median (IQR) FIO2 of 0.6 (0.5-0.6) and mean positive end-expiratory pressure (PEEP) of 10.8+or-2.3 cmH₂O. The most prevalent comorbidities were arterial hypertension (44.0%), diabetes (22.9%), ischaemic cardiac disease (17.2%) and chronic arrhythmia (10.8%). Hypoxaemia generally improved when CPAP treatment was initiated: median (IQR) values of PaO2/FIO2 ratio at baseline on oxygen therapy (142.9 (96.7-203.2)) significantly improved when helmet CPAP was used after 6 h (205.6 (140.0-271.1), p<0.0001). However, an increase of at least 30% in PaO2/FIO2 ratio during helmet CPAP application in comparison to oxygen therapy was found only in 52% of the population. Median (IQR) duration of helmet CPAP treatment was 6 days. Only 4 patients discontinued helmet CPAP because of intolerance. CPAP failure was observed in 70 (44.6%) patients: 34 (21.7%) were intubated and 36 (22.9%) died during the HDU stay. 87 (55.4%) patients improved during the HDU stay, weaned to oxygen therapy and transferred to the general ward. No patients were intubated during the first hours after CPAP initiation or under high emergency conditions. Among those who died in HDU, pneumonia-related deaths were detected in 26 patients, while non-pneumonia related in 10 patients, including pulmonary embolisms (n=5), end-stage renal failure (n=2), cerebrovascular accident (n=1), end-stage heart failure (n=1) and septic shock (n=1). Among the 34 patients who were intubated in HDU and transferred to the ICU, nine (26.5%) died. A total of 65 (41.4%) patients had a Do-Not-Intubate (DNI) status on HDU admission: 36 died and 29 survived. At the multivariable analysis, CPAP failure was associated with the severity of pneumonia on admission (HR (95% CI) 2.9 (1.3-6.2), p=0.009) and higher baseline values of interleukin-6 (HR (95% CI) 1.0 (1.0-1.0), p<0.009). The all-cause in-hospital and 30-day mortality rates were 28.7% and 28.0%, respectively.

Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.